Silk is a naturally occurring polymer and it remains a notable biomaterial for use in pharmaceutical and biomedical applications due to its unique mechanical and physicochemical properties. Silk proteins provide versatile structural frameworks for encapsulating diverse therapeutic agents due to their amphiphilic nature and β-sheet driven stability. A variety of fabrication techniques enable precise control over particle size, morphology and drug release kinetics. Hybrid silk-polymer composites i.e., integrating silk proteins with biopolymers like PEG, PVA and chitosan further optimize mechanical properties and enhance bioactivity. Various silk sources, including Antheraea species and recombinant spider silk contribute to the expanding applications of various drugs delivery systems (DDS). Silk-based nanocarriers offer an attractive alternative for sustained and localized drug administration due to their non-toxic degradation products. Despite their advantages, challenges such as largescale production, stability and precise drug release mechanisms remain areas of active research. Knowing the characteristics of silk proteins and the possible methods for modifying their arrangement enables the ability to create tweaked DDS with the anticipated outcomes. Chapter covers aspects on design, production, benefits, and biomedical applications of silk protein-based nano-carriers, highlighting their role in revolutionizing drug delivery strategies. Further research into optimizing their performance could lead to widespread clinical applications offering safer and more effective treatment options.