Topical delivery of medicaments in a controlled manner is still a promising area of research. Drug-containing dammar gum-ethyl cellulose composite microsponge loaded gel formulation (D-MSPG) was developed for controlled topical delivery of mupirocin. The drug-loaded microsponges (D-MSPs) were formulated by the quasi-emulsion solvent diffusion method and were evaluated for morphology, particle size distribution, entrapment efficiency, thermal properties, and crystallinity. The optimized D-MSPs (entrapment efficiency 91.5 ± 4.0% and particle size of 55.15 ± 2.9 μm) were dispersed in carbopol 934 gel (D-MSPG). The final product was characterized for pH, viscosity, texture, spreadability, consistency, syneresis, in vitro drug release, and ex vivo skin penetration study. A comparative study with marketed formulation was performed. For optimized gel formulation (G4), drug content was 104.19 ± 1.68%, and drug release was 84.19% after 24 h. The pH of the optimized gel was observed to be 6.05 ± 0.04. Viscosity of the optimized gel formulation was found to be 1212.15 ± 434.85 mPa-s at 50 s⁻¹. The steady-state flux (J) in ex vivo skin permeation was observed to be 53.96 μg cm⁻² h⁻¹ and the permeability coefficient was 2.69 cm/h for the optimized gel formulation. According to the findings, the D-MSPG-based formulation strategy can act well to prolong the topical delivery of mupirocin or similar drug molecules.