2.1. Early Uses of Natural Pesticides in Agriculture

The use of natural pesticides in agriculture can be traced back to ancient civilizations, where farmers relied on nature’s resources to protect their crops. Ancient Egyptians utilized garlic and onion extracts as insect repellents, demonstrating an intuitive understanding of plant-derived bioactive compounds. In China, chrysanthemum flowers rich in pyrethrins were employed to combat crop-damaging pests, an approach that remains relevant in modern pest control practices [3]. These early techniques were innovative for their time and showcased humanity’s ability to harness nature for sustainable agricultural practices, even without scientific knowledge.

2.2. Transition From Natural to Synthetic Pesticides

As agricultural demands intensified during the Industrial Revolution, the limitations of natural pesticides became apparent. Extracting bioactive compounds was labor-intensive, and variability in efficacy posed challenges for large-scale applications. This led to the advent of synthetic pesticides, such as dichlorodiphenyltrichloroethane (DDT), which improved pest management. During World War II, DDT offered unprecedented efficiency, uniformity, and scalability compared to natural alternatives [18]. However, this transition marked a key moment in agriculture, where pursuing higher yields began to outweigh ecological considerations.

The widespread use of synthetic pesticides came with consequences. Issues such as bioaccumulation in the food chain, environmental contamination, and pest resistance emerged as significant challenges. Public awareness of these risks gained momentum following the publication of Rachel Carson’s Silent Spring, highlighting the environmental damage caused by synthetic pesticides and spurred regulatory changes [19]. Despite their transformative impact on agriculture, synthetic pesticides underscored the need for a balance between productivity and sustainability.

2.3. Limitations of Traditional Approaches

While natural pesticides are environmentally friendly, they face several inherent limitations. Their reliance on environmental stability means external factors like temperature, humidity, and UV exposure can degrade their efficacy. For instance, neem-based pesticides have shown great potential in controlled conditions but often fail to perform consistently in the field [20]. Additionally, natural pesticides exhibit narrow-spectrum activity, necessitating combinations to target multiple pests. These limitations made them less practical for large-scale use, particularly in industrial agriculture.

Despite addressing scalability and efficacy issues, synthetic pesticides introduced their own set of problems. Overuse and improper application led to developing pesticide-resistant pests and ecological imbalances. Furthermore, synthetic pesticides frequently harmed nontarget species, contributing to biodiversity loss. These challenges emphasized the need for innovative approaches that could combine natural pesticides’ ecological benefits with synthetic solutions’ stability and effectiveness.

2.4. Historical Milestones in Natural Pesticides Development

The timeline traces the evolution of natural pesticides, beginning in the 1900s when farmers relied on traditional plant-based remedies for pest control, reflecting centuries of knowledge passed down through generations [21]. By the 1920s, scientific advancements led to the isolation of pyrethrins from chrysanthemum flowers, marking the first step in understanding the potential of natural bioactives for targeted pest control. In the 1940s, the development of synthetic pesticides like DDT marked a transformative shift, offering scalable and effective solutions while diverting attention from natural pest control methods [22]. In the 1960s, Rachel Carson’s Silent Spring highlighted the ecological risks of synthetic pesticides, prompting renewed interest in safer alternatives [19]. The 1970s marked a significant moment with the global recognition of neem as an eco-friendly and sustainable pesticide. In the 1980s, integrated pest management (IPM) emerged, emphasizing a balanced use of synthetic and natural methods to reduce environmental impact [23]. The 1990s brought advances in biotechnology, with genetically engineered crops like those producing Bacillus thuringiensis (Bt) toxins demonstrating the integration of bioengineering in pest management [24]. The 2000s saw global policies restricting harmful synthetic pesticides, driving innovation in biopesticides and natural alternatives aligned with sustainability goals [25]. During the 2010s, biomimetic approaches gained prominence, with scientists designing nature-inspired solutions to enhance the stability and efficacy of natural pesticides. By the 2020s, technologies such as nanotechnology and advanced formulations optimized natural pesticides, establishing their role in sustainable agriculture and IPM systems. Figure 1 illustrates the evolution of natural pesticides, a historical journey from traditional practices to cutting-edge sustainable solutions in agricultural pest management.

3.1. Principles of Biomimicry in Pesticide Design

Biomimicry in pesticide design harnesses mechanisms evolved in nature to develop precise, sustainable, and ecologically aligned pest control strategies. A prominent example is azadirachtin, a bioactive compound derived from the neem tree (Azadirachta indica), which disrupts insect growth and reproduction by interfering with hormonal regulation. Similarly, pyrethrins, extracted from chrysanthemum flowers (Chrysanthemum cinerariifolium), target the insect nervous system, causing paralysis and death with minimal impact on mammals and beneficial species [26]. These examples reflect how biomimetic pesticides achieve high specificity, reducing collateral damage to nontarget organisms. In addition to biochemical mimicry, recent advances also explore structural inspirations from nature. For instance, the micro- and nanoscale architecture of insect cuticles has inspired the design of interface materials that enhance pesticide adhesion and controlled delivery, improving efficacy while minimizing runoff and environmental exposure [27].

Biomimetic pesticide designs also prioritize biodegradability, ensuring active agents break down naturally in the environment, thereby reducing ecological disruption and chemical persistence [28]. Integrating computational biology and artificial intelligence (AI) further accelerates this process. These tools enable modeling natural compound interactions with pest targets, facilitating the design of synthetic analogs that replicate natural efficacy with improved stability or delivery properties [29]. Biomimicry offers a holistic framework for pesticide development that draws from biochemical, structural, and ecological cues in nature. It fosters innovation that is precise, adaptive, and sustainable. Figure 2 illustrates the cycle of biomimetic pesticide development in a holistic process inspired by nature that emphasizes the development of natural compounds, ensures specificity, achieves sustainability, leverages AI tools, and addresses agricultural challenges.

3.2. Case Studies of Biomimetic Natural Pesticides

3.2.2. Pyrethroids Derived From Chrysanthemum

Inspired by natural pyrethrins extracted from chrysanthemum flowers, pyrethroids represent another landmark achievement in biomimetic pesticide design [32]. Pyrethrins act on insect nervous systems, leading to paralysis and eventual death, while exhibiting low toxicity to mammals. Synthetic pyrethroids, modeled after natural pyrethrins, have enhanced stability and extended shelf life, overcoming the natural degradation challenges of pyrethrins. However, the overuse of synthetic pyrethroids has contributed to pest resistance, highlighting the need for responsible usage and further refinement of biomimetic strategies [33].

Nagar et al. demonstrated the effectiveness of various extraction and enrichment techniques for isolating pyrethrins, the active insecticidal compounds derived from Chrysanthemum cinerariaefolium [34]. They found that pyrethrins act by targeting the insect nervous system, causing rapid paralysis and eventual death, a mechanism that reflects their high specificity and low mammalian toxicity. Among the extraction methods tested, the Soxhlet technique using methanol provided the highest yield. At the same time, acetonitrile was the most effective solvent for enrichment, achieving pyrethrin concentrations of up to 60.37% through solid-matrix partitioning. Their study emphasized the environmental benefits of these natural compounds in organic farming and IPM systems. The insecticidal properties of pyrethrum extract arise from six compounds, all of which share a characteristic stereochemical configuration, as illustrated in Figure 3.

3.3. Mechanisms of Action: Mimicking Nature’s Strategies

Biomimetic pesticides mimic nature’s precision and efficacy in pest control. Azadirachtin, a tetranortriterpenoid compound extracted from the seeds and leaves of the neem tree (Azadirachta indica), is renowned for its multifaceted insecticidal properties [35]. It primarily disrupts the endocrine system of insects, mainly through interference with the production and activity of ecdysone, a hormone critical for molting and metamorphosis [36]. This disruption halts the growth and development of larvae, preventing them from reaching maturity. Azadirachtin also inhibits the synthesis of juvenile hormones, which are essential for maintaining normal insect development and reproductive processes. This dual interference in hormonal regulation prevents insects from progressing through their life cycle stages, effectively controlling their populations. In addition to its effects on hormonal pathways, azadirachtin acts as a potent antifeedant, deterring insects from consuming treated plants. It achieves this by disrupting the neurosensory functions associated with feeding, leading to reduced nutrient intake and eventual starvation. Furthermore, azadirachtin has been shown to impair oviposition in female insects by disrupting egg-laying behavior and reducing the viability of laid eggs.

One of the most significant advantages of azadirachtin is its specificity; it selectively targets the physiological pathways of insect pests while leaving nontarget organisms such as pollinators, earthworms, and other beneficial species unharmed. This makes it an invaluable component in IPM systems [37]. Its natural origin and rapid biodegradability also minimize environmental persistence and reduce the risk of bioaccumulation, aligning with sustainability goals in agriculture. These properties investigate azadirachtin’s potential as a cornerstone for eco-friendly pest management practices in modern farming systems. Figure 4 represents the mechanism of action of azadirachtin as a natural pesticide.

Pyrethrins, derived from chrysanthemum flowers (Chrysanthemum cinerariaefolium), are natural insecticidal compounds that target voltage-gated sodium ion channels in insect neurons [38]. By prolonging the open state of these channels, pyrethrins disrupt the normal flow of sodium ions across the neuronal membrane, causing hyperexcitation of the nervous system [39]. This leads to paralysis and eventual death of the insect. Known for their rapid knockdown effect, pyrethrins are highly effective against various pests. Their low affinity for mammalian sodium channels ensures safety for humans and nontarget species. Unlike synthetic pesticides, pyrethrins degrade quickly in sunlight and air, reducing environmental persistence and contamination risks. This biodegradability makes them a valuable component of organic farming and IPM systems. However, their susceptibility to UV degradation can limit field efficacy, necessitating improved formulations. Pyrethrins exemplify the potential of natural compounds for eco-friendly pest control, balancing efficacy with environmental safety. Figure 5 illustrates the mechanism of action of pyrethrins, derived from chrysanthemum flowers.

3.4. Sustainability Impacts of Biomimetic Approaches

Biomimetic pesticides significantly contribute to environmental sustainability by aligning with natural ecological processes. Their reduced persistence in the environment minimizes risks of bioaccumulation and contamination in water bodies. Additionally, biomimetic pesticide production often employs greener chemistry, avoiding toxic solvents and reducing waste. For instance, recent advancements in the extraction and formulation of neem and pyrethrin-based pesticides have lowered their environmental impact and carbon footprint [40]. By emulating nature, biomimetic approaches inherently support ecological balance while meeting the demands of modern agriculture. Biomimetic advances in pesticide development showcase the potential to harmonize efficacy with sustainability. These innovations provide transformative solutions to contemporary agricultural challenges, fostering a future where productivity and ecological preservation coexist. Continued investment in biomimetic research is essential to realizing the full potential of these groundbreaking strategies. Table 1 provides a detailed comparison of biomimetic and synthetic pesticides across key sustainability and functional aspects.

4.1. Evolution of Synthetic Techniques Inspired by Nature

The evolution of synthetic techniques in pesticide development has been profoundly influenced by natural bioactive compounds, which serve as structural and functional templates for chemical innovation. These efforts aim to replicate and enhance nature’s efficacy, selectivity, and ecological safety in pest control agents. A well-established example is the development of pyrethroids, synthetic analogs of pyrethrins—insecticidal esters derived from Chrysanthemum flowers. While natural pyrethrins are effective but photolabile, pyrethroids incorporate structural modifications to improve thermal and photostability, resulting in prolonged field efficacy and reduced application frequency [41]. Advancements in molecular modeling and structure–activity relationship (SAR) analysis further drive the rational design of synthetic pesticides. These computational tools facilitate the development of derivatives with enhanced pest specificity and environmental resilience, allowing researchers to simulate molecular interactions and optimize binding affinities before synthesis [42]. For example, cyclopropane-based structures, known for their rigid triangular geometry and conformational stability, have been increasingly incorporated into pesticide molecules to enhance target specificity, chemical durability, and resistance to metabolic degradation. The cyclopropane moiety acts as a conformational lock, mimicking the compact, active-site-binding features found in certain natural compounds. Recent studies demonstrate that cyclopropane-containing synthetic pesticides exhibit improved biological activity and reduced volatility, making them promising candidates for durable pest control solutions [43]. These biomimetic strategies highlight the role of nature-inspired chemical design in advancing modern, sustainable pesticide technologies.

4.2. Hybrid Pesticides: Combining Natural and Synthetic Features

Hybrid pesticides, which integrate natural and synthetic components, is a promising solution to address the limitations of traditional natural pesticides and conventional synthetics. These formulations leverage the bioactivity of natural compounds while incorporating synthetic enhancements to improve stability, scalability, and efficacy. A notable example is the development of hybrid formulations combining neem oil with synthetic stabilizers to counteract its rapid degradation under UV light, significantly extending its field effectiveness [44, 45]. Another breakthrough involves hybrid formulations of pyrethroids, which combine the fast action of natural pyrethrins with synthetic modifications to prevent pest resistance. These hybrid approaches underscore the potential to harmonize the strengths of natural and synthetic methodologies, offering versatile tools for sustainable pest management. However, careful regulation and monitoring are essential to maintain these formulations’ environmental compatibility.

4.3. Advances in Green Chemistry for Pesticide Synthesis

Green chemistry has played a pivotal role in transforming synthetic pesticide production, emphasizing sustainability, efficiency, and safety. Innovations in solvent-free synthesis, catalysis, and energy-efficient processes have minimized the environmental impact of pesticide manufacturing. For example, using ionic liquids and water-based reactions in pyrethroid synthesis has significantly reduced the reliance on hazardous organic solvents, aligning production processes with green chemistry principles [46–48]. Similarly, the integration of renewable feedstocks, such as plant-based raw materials, has further reduced the carbon footprint of synthetic pesticide production. Advanced catalytic systems, including enzyme-based and nanoparticle catalysts, have enabled selective synthesis of pesticide molecules, minimizing waste, and improving reaction yields. Figure 6 highlights key advancements in green chemistry for pesticide synthesis, including solvent-free methods using ionic liquids and water-based reactions to reduce hazardous solvents, renewable feedstocks to lower carbon footprints, and advanced catalytic systems like enzyme-based and nanoparticle catalysts for selective synthesis, all of which minimize waste, improve reaction yields, and promote sustainable, eco-friendly agricultural practices.

4.4. Challenges in Scaling Synthetic Natural Pesticides

Despite significant progress, scaling synthetic natural pesticides for widespread agricultural use remains a complex challenge. One of the primary obstacles lies in balancing production costs with affordability for farmers. While green chemistry processes are environmentally advantageous, they often involve higher initial investment and operational complexity, limiting their adoption in resource-constrained regions [49]. Additionally, achieving consistency in synthesizing complex biomimetic compounds requires advanced technologies and rigorous quality control measures, further reducing production costs. Regulatory hurdles, particularly in the approval and testing phases, impede innovative pesticides’ rapid deployment. Furthermore, ensuring that synthetic derivatives maintain the ecological benefits of their natural counterparts while avoiding unintended impacts on nontarget species poses a critical scientific and ethical challenge.

To overcome these challenges, interdisciplinary collaboration between chemists, biologists, and agricultural engineers is essential. Investments in research and development, coupled with supportive policy frameworks, can accelerate the scalability of synthetic natural pesticides, bridging the gap between laboratory innovation and field application. These efforts hold the potential to redefine pest management practices, aligning agricultural productivity with ecological sustainability. Table 2 outlines the key challenges in scaling synthetic natural pesticides, including high production costs, operational complexity, consistency in synthesis, regulatory hurdles, ecological compatibility, and limited adoption in resource-constrained regions.

5.1. Efficacy in Pest Control

Biomimetic pesticides, derived from natural compounds, exhibit highly targeted action by mimicking biological molecules that disrupt pest-specific pathways. Azadirachtin disrupts hormonal systems, while pyrethrins target sodium ion channels, leading to paralysis and death in pests [50, 51]. These mechanisms often ensure high specificity, reducing harm to nontarget organisms. However, their rapid degradation under environmental conditions, such as sunlight and microbial activity, can limit their field longevity, necessitating frequent applications or improved formulations. In contrast, synthetic pesticides, designed for durability and broad-spectrum efficacy, can provide prolonged pest control with fewer applications. For example, synthetic pyrethroids offer enhanced stability and a longer residual effect than their natural counterparts. While this ensures consistent pest suppression, it also increases the likelihood of pest resistance over time, a growing concern in agricultural practices. Balancing these attributes, biomimetic approaches are increasingly integrated into pest management systems to complement synthetic methods, creating a synergistic strategy for sustained efficacy.

5.2. Environmental and Ecotoxicological Impacts

Biomimetic pesticides have a clear advantage when it comes to environmental compatibility. Being biodegradable and naturally occurring, they minimize risks of environmental persistence and bioaccumulation. For example, neem-based formulations rapidly degrade into nontoxic residues, ensuring minimal contamination of soil and water bodies [52, 53]. Additionally, their specificity spares beneficial organisms, such as pollinators and natural predators, promoting ecological balance. However, the challenge lies in maintaining efficacy under varying field conditions, where degradation may occur too quickly to provide effective pest control. Conversely, synthetic pesticides often persist in the environment for extended periods, leading to concerns about long-term contamination. Persistent organic pollutants (POPs) from synthetic pesticides can accumulate in ecosystems, affecting nontarget species and disrupting ecological networks. For instance, studies have linked synthetic pesticide runoff to declines in aquatic biodiversity and the contamination of groundwater supplies [54–57]. The trade-off between durability and environmental safety highlights the need for regulatory frameworks to limit the use of highly persistent synthetic pesticides while incentivizing biomimetic alternatives.

5.3. Cost-Effectiveness and Accessibility

The economic considerations of pesticide adoption are critical for widespread use, particularly in resource-constrained regions. Synthetic pesticides are generally more cost-effective initially, benefiting from economies of scale in production and distribution. Their durability reduces the need for frequent reapplications, lowering operational costs for farmers. However, the long-term costs associated with environmental remediation, pest resistance management, and health risks often outweigh these initial savings [58–60]. Biomimetic pesticides, while environmentally advantageous, often face higher production costs due to the complexity of extracting and synthesizing natural compounds. For example, azadirachtin extraction from neem or the synthesis of pyrethrin analogs requires advanced technologies and precision processes, increasing their market price. Despite this, their alignment with sustainable farming practices and reduced environmental liabilities makes them a cost-effective solution in the long term. Subsidies, governmental incentives, and advancements in green chemistry are essential to bridge the affordability gap and make biomimetic pesticides accessible to smallholder farmers [61–63].

5.4. Long-Term Impacts on Soil and Ecosystems

The long-term impacts of pesticide usage on soil health and ecosystem functionality further distinguish biomimetic and synthetic approaches. Due to their biodegradability, biomimetic pesticides have minimal residual effects on soil microorganisms and fertility. For instance, neem-based formulations have been shown to enhance soil health by promoting beneficial microbial activity and reducing harmful pathogens [64]. Similarly, using pyrethrin-based products has limited negative effects on earthworm populations and other essential soil fauna, preserving ecosystem services vital for sustainable agriculture. On the other hand, synthetic pesticides can disrupt soil ecosystems by accumulating toxic residues. Prolonged use of such chemicals often leads to the suppression of beneficial microbes, soil acidification, and reduced fertility. Furthermore, the unintended impacts on nontarget organisms, such as earthworms and nitrogen-fixing bacteria, can diminish soil productivity over time [65–67]. These ecological consequences highlight the importance of transitioning to biomimetic solutions to preserve soil and ecosystem health while maintaining agricultural productivity. Table 3 provides a detailed and inclusive comparison between biomimetic and synthetic approaches in natural pesticides across critical aspects such as efficacy, environmental impacts, cost, scalability, and regulatory processes.

6.1. Key Challenges in Achieving Sustainability

Achieving sustainability in pesticide development and use requires addressing multifaceted environmental, economic, and operational challenges. One significant issue is the environmental persistence of synthetic pesticides, which contributes to soil degradation, water contamination, and bioaccumulation in nontarget organisms. Despite the potential of biomimetic pesticides to mitigate these impacts, their adoption faces hurdles such as higher production costs, limited scalability, and variability in field performance. For example, while eco-friendly, neem-based pesticides often degrade rapidly under ultraviolet light, reducing their efficacy in open agricultural environments [68]. Additionally, resistance management remains a critical concern, as pests can evolve mechanisms to counteract natural and synthetic pesticides, necessitating ongoing innovation in design and delivery mechanisms [69–71]. Economic barriers also persist, especially for small-scale farmers in resource-limited settings who may lack access to affordable, sustainable pesticides. Bridging these gaps requires a systemic approach integrating technological advancements, financial incentives, and targeted education programs to promote sustainable practices while maintaining agricultural productivity. Figure 7 illustrates the critical challenges in achieving sustainable pesticide development, represented as the roots of a tree to signify foundational barriers.

6.2. Innovations in Delivery Mechanisms

Advancements in delivery mechanisms are critical to improving the efficacy, environmental stability, and targeted action of natural pesticides. Traditional formulations often suffer from rapid degradation, uncontrolled dispersion, and reduced field performance. Recent innovations—particularly in nano- and microencapsulation technologies—have improved pesticide delivery systems by offering protection and precision. One strategy is using polymeric nanoparticles (e.g., PLGA, chitosan, alginate), encapsulating active ingredients like azadirachtin and enabling slow, controlled release. For example, azadirachtin-loaded chitosan nanoparticles (size ∼150 nm) have shown enhanced UV stability and a 2.5-fold increase in residual activity compared to nonencapsulated formulations.

Another technique involves liposomal encapsulation, where lipids form bilayer vesicles that encapsulate hydrophobic and hydrophilic pesticides. Liposomal pyrethrin formulations have demonstrated improved dispersion in aqueous media and delayed release, extending field efficacy to over 10 days under standard agricultural conditions. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are also gaining attention (Figure 8) [72]. SLN-based delivery of neem oil has improved adherence to plant surfaces and increased larvicidal activity by over 40% in Spodoptera litura infestations [73–75]. In addition, smart delivery systems have emerged, leveraging stimuli-responsive materials that release active agents in response to environmental triggers such as pH, temperature, or humidity. For instance, pH-sensitive silica-based nanocarriers functionalized with polydopamine have been used to release pesticide only in the alkaline pH of insect midguts, thereby reducing nontarget exposure [76–78].

Zhao et al. developed a pH-responsive nanopesticide using hollow mesoporous silica nanoparticles loaded with prochloraz and capped with ZnO quantum dots, achieving controlled release, enhanced photostability, and systemic delivery in rice plants (Figure 9) [79]. The nanoformulation showed 2.67-fold higher release under acidic conditions and demonstrated effective fungicidal activity against rice blast disease, highlighting its potential in precision agriculture. These delivery systems not only reduce the frequency of application but also minimize pesticide leaching and environmental persistence, aligning with the goals of sustainable and precision agriculture. Integrating these novel systems represents a shift from conventional pesticide delivery to next-generation biomimetic formulations that are smarter, safer, and more effective.

6.3. Role of Biotechnology and Nanotechnology

Biotechnology and nanotechnology are transforming the landscape of pesticide development by providing tools for designing highly specific, environmentally safe, and effective solutions. Biotechnology enables genetically engineering crops that produce natural pesticides, such as Bt toxins, directly within their tissues. These genetically modified organisms (GMOs) reduce the need for external pesticide applications while precisely targeting specific pests. However, concerns about ecological impacts and public acceptance necessitate robust regulatory frameworks and transparent communication strategies [80, 81]. Nanotechnology complements these efforts by enhancing the formulation and delivery of pesticides. Nanoemulsions, nanosuspensions, and nanocarriers improve active ingredient solubility, stability, and bioavailability, resulting in more efficient pest control. For example, silver nanoparticles have been investigated for their dual roles as antimicrobial agents and carriers for natural pesticide compounds, providing a synergistic approach to pest and pathogen management [82–84]. These cutting-edge technologies underscore the transformative potential of interdisciplinary research in addressing the dual challenges of efficacy and sustainability.

6.4. Policy and Regulatory Considerations

Policy and regulatory frameworks are indispensable in bridging the gap between efficacy and sustainability in pesticide use. A major challenge lies in establishing globally harmonized standards that balance innovation with safety and environmental protection. Current regulatory processes often involve lengthy approval timelines, particularly for novel biomimetic and nanotechnology-based pesticides, which can hinder their timely adoption [85]. Simplifying these processes while ensuring rigorous safety evaluations is essential for promoting sustainable alternatives. Policies incentivizing the development and adoption of eco-friendly pesticides can accelerate the transition toward sustainability. Subsidies, tax breaks, and research grants for companies and researchers working on biomimetic and green chemistry-based solutions can significantly reduce the financial barriers to innovation. Public awareness campaigns and farmer education programs are equally important to encourage the widespread use of sustainable practices, bridging the gap between laboratory advancements and field application [86].

7.1. Agricultural Applications: Field Studies and Case Examples

The practical implementation of biomimetic and synthetic pesticides has shown significant promise in diverse agricultural settings. Field studies have demonstrated the efficacy of neem-based pesticides in controlling aphids, whiteflies, and other sap-sucking pests in crops such as potatoes, wheat, peach, chili, okra, cotton, tomatoes, and mangoes (Table 4). Similarly, pyrethrin-based formulations have proven effective in managing fruit fly populations in orchards, with minimal environmental residues, ensuring compliance with export standards [99]. Synthetic pesticides, such as pyrethroids, have also been extensively utilized in large-scale agriculture due to their broad-spectrum activity and residual efficacy [100]. Nizam et al. reported that pyrethroids effectively controlled pests like planthoppers in Southeast Asian rice fields, improving yields. However, improper handling and disposal led to environmental contamination and ecological risks, particularly to aquatic organisms, emphasizing the need for sustainable pesticide practice [101]. These examples underscore the need for a balanced integration of biomimetic and synthetic approaches to optimize productivity and sustainability. Table 4 summarizes the major findings from multiple studies on neem-based and other biopesticides, highlighting their effectiveness against various pests and crops, specific mechanisms of action, and contributions to sustainability.

7.2. Applications in IPM

Biomimetic and synthetic pesticides are increasingly being integrated into IPM programs to achieve sustainable pest control [102, 103]. IPM emphasizes using multiple control strategies, including biological, cultural, and chemical methods, to minimize pest populations while reducing reliance on synthetic chemicals. Biomimetic pesticides, such as neem and Bt-based formulations, target specific pests without disrupting natural predators or beneficial organisms. For instance, in maize cultivation, incorporating Bt sprays into IPM strategies effectively controlled corn borers while maintaining ecological balance [104]. Synthetic pesticides, while not entirely excluded from IPM programs, are used judiciously to manage outbreaks that exceed the control capacity of natural methods. For example, the selective use of synthetic pyrethroids in conjunction with pheromone traps and biological controls has successfully reduced pest damage in vineyards [105]. This integrated approach minimized chemical usage and enhanced the effectiveness of natural pest control agents [106, 107]. The synergy between biomimetic and synthetic pesticides within IPM frameworks demonstrates their potential to harmonize efficacy with environmental stewardship.

7.3. Commercial Success Stories of Biomimetic and Synthetic Pesticides

The commercialization of biomimetic and synthetic pesticides has led to several notable success stories, reflecting their market viability and agricultural impact. Neem-based products, such as azadirachtin EC formulations, have gained widespread acceptance in organic farming due to their eco-friendly profile and effectiveness against various pests [108, 109]. The commercial success of a leading neem pesticide brand in Europe has been attributed to its compatibility with organic certification standards and its ability to meet consumer demand for residue-free produce [110–112]. Synthetic pesticides have also achieved significant commercial milestones, particularly in large-scale industrial farming. Pyrethroid-based products, such as deltamethrin and lambda-cyhalothrin, are among the most widely used synthetic pesticides globally, with applications ranging from cotton to vegetable crops [113, 114]. Their broad-spectrum activity, cost-effectiveness, and long-lasting field performance drive their success. However, the increasing regulatory restrictions on synthetic pesticides in regions like the European Union have prompted companies to invest in greener, biomimetic alternatives, signaling a shift toward sustainability [115].

8.1. Emerging Technologies in Pesticide Design

The future of natural pesticide development lies in leveraging advanced technologies to enhance efficacy, specificity, and environmental sustainability. One promising avenue is using nanotechnology to create novel formulations that improve the delivery and stability of active compounds. For instance, nanoencapsulation techniques can protect bioactive ingredients like azadirachtin from rapid degradation under UV light, ensuring prolonged effectiveness in field applications [116, 117]. Additionally, smart pesticides incorporating responsive systems that release active ingredients based on environmental triggers such as pH, humidity, or temperature are gaining traction as cutting-edge solutions to reduce waste and environmental impact [118–120]. AI and machine learning are also set to revolutionize pesticide design by enabling predictive modeling of compound efficacy, optimizing formulations, and identifying potential resistance pathways [121, 122]. These technologies, combined with advances in bioinformatics, allow for the discovery of new bioactive molecules from natural sources, accelerating innovation in biomimetic pesticide development [123].

8.2. Synergies Between Biomimetic and Synthetic Approaches

Biomimetic and synthetic approaches, often seen as competing methodologies, have the potential to complement each other when strategically integrated. Biomimetic pesticides excel in their ecological compatibility and specificity, while synthetic pesticides offer durability and broad-spectrum efficacy. Combining these strengths can lead to hybrid formulations that maximize pest control while minimizing environmental risks. The synthetic analogs of natural compounds, such as pyrethroids derived from pyrethrins, provide enhanced stability without compromising biodegradability [114]. Moreover, integrating biomimetic pesticides into synthetic-dominated IPM systems can enhance the overall sustainability of pest control practices. Their treatments can be paired with reduced doses of synthetic chemicals to maintain pest populations below economic threshold levels while reducing the likelihood of resistance development and environmental contamination [80, 124].

8.3. Interdisciplinary Research and Collaboration Opportunities

The development of next-generation natural pesticides demands interdisciplinary collaboration, bringing together expertise from chemistry, biology, nanotechnology, data science, and agricultural engineering. Chemists and biologists can work on isolating and synthesizing bioactive molecules, while engineers develop advanced delivery mechanisms to enhance field performance. For example, collaborations between agricultural researchers and materials scientists have already resulted in biodegradable polymers for encapsulating active ingredients, ensuring targeted release and reduced environmental residue [125]. Public–private partnerships also have the potential to accelerate innovation by pooling resources and expertise. Companies investing in sustainable agricultural solutions can collaborate with academic institutions to test new formulations in real-world conditions, bridging the gap between laboratory research and commercial application. Funding agencies and policymakers must prioritize these collaborations by offering incentives for projects focused on ecological pest control [126].

8.4. Anticipating Future Challenges and Solutions

As the demand for sustainable pest management grows, the natural pesticide industry must address several challenges to maintain its trajectory of innovation. A critical issue is the scalability of natural pesticide production, particularly in resource-constrained regions where access to technology and capital is limited. Addressing this requires investment in cost-efficient production methods, such as using renewable feedstocks and green chemistry techniques to lower manufacturing expenses [11]. Another pressing challenge is the evolution of pest resistance, which threatens the long-term efficacy of both biomimetic and synthetic pesticides. Solutions include rotating active ingredients with diverse mechanisms of action, deploying combination treatments, and integrating pest monitoring technologies to ensure timely interventions [127]. Finally, navigating regulatory landscapes remains complex, particularly for novel biomimetic products that straddle the boundaries of biological and chemical classifications. Harmonizing international standards and expediting approval processes while maintaining rigorous safety evaluations will be critical for promoting global adoption [128]. Table 5 comprehensively addresses the critical challenges and proposed solutions while emphasizing their sustainability impact.