Amphiphilic peptides have garnered significant attention due to their highly designable and self-assembling behaviors. Self-assembled peptides hold excellent potential in various fields such as biosensing, environmental monitoring, and drug delivery, owing to their remarkable biological, physical, and chemical properties. While nanomaterials formed by peptide self-assembly have found widespread use in biomedical applications, the development of 2D peptide nanosheets based on the self-assembly of amphiphilic peptides remains challenging in terms of rational design and morphology modulation. In this study, rationally designed amphiphilic peptide molecules are self-assembled into peptide nanosheets (PNS) under specific conditions to encapsulate gold nanoparticles (AuNPs), resulting in the formation of AuNPs/PNS hybrid materials with high photothermal conversion efficiency. The findings demonstrate that 2D PNS enhances the overall photothermal therapy effect of the nanohybrid materials due to their larger hosting area for AuNPs and higher biocompatibility. The well-designed amphiphilic peptides in this study offer insights into the structural design and functional modulation of self-assembled molecules. In addition, the constructed biomimetic-functional 2D inorganic/organic nanohybrid materials hold potential applications in biomedical engineering.