Objective: The purpose of the present study aims to design a novel drug delivery system containing clarithromycin microsponges and to prepare microsponge gel. Methods: The microsponges were prepared by quasi-emulsion solvent diffusion method using polymer eudragit RS-100. All the formulated microsponges were subjected to various evaluation parameters such as production yield, encapsulation efficiency, particle size analysis, and in vitro drug release study. Results: In vitro drug release of all the formulations was found to be 47.36% to 87.32%. Formulations F2, F3, and F4 show the best drug release from all formulations within 480 min. The optimized microsponge formulations F2, F3, and F4 were further formulated as gel formulations for topical delivery. Prepared gel was evaluated for physical parameters like pH, spreadability, viscosity, drug content, in vitro diffusion study, and stability study. All gel formulations showed drug release of 63.18±0.52%, 76.4±0.51%, and 72.93±0.42% from formulations GF1, GF2, and GF3, respectively, within 480 min. The microsponge gel formulation GF2 showed the controlled release of clarithromycin for 480 min, which was 76.4±0.51%. The stability study shows no significant changes in all parameters. Conclusion: With the revealed results by different evaluation parameters, it is concluded that the microsponges drug delivery system has become a highly competitive and rapidly evolving technology and more and more research is carried out to optimize the cost-effectiveness and efficacy of the therapy.