Sericin, a glycoprotein derived from silk cocoons, has gained significant attention as a versatile biomaterial for drug delivery due to its biocompatibility, biodegradability, and amphipathic nature. This review explores recent advancements in sericin-based drug delivery systems across three key therapeutic domains: antimicrobial applications, anticancer treatments, and neurodegenerative diseases. Various fabrication techniques, including nanoparticles, hydrogels, and microneedles, have been investigated to optimize drug encapsulation, targeted release, and bioavailability. While sericin holds great promise for overcoming challenges associated with synthetic polymers, issues such as molecular variability, formulation stability, and regulatory considerations remain critical hurdles. Future research should focus on optimizing sericin extraction methods, enhancing structural stability, and integrating it with cutting-edge biomedical technologies to maximize its therapeutic efficacy.