Silk is a protein-based natural biopolymer produced from the modified labial glands called silk glands by the domesticated silkworm, Bombyx mori. The secreted silk is stored in the lumen of the gland and spun as fiber by the spinneret. Silk is composed of mainly two proteins, fibroin and sericin. Silk has gained popularity in many medical and pharmaceutical applications due to its biocompatibility, biodegradability, and versatility. These attributes made silk a polymer matrix in the nanocomposites. Nanocomposites are materials prepared by mixing polymers with nanoparticles. Incorporating metals and metal oxides nanoparticles of into silk protein-based polymer was shown to be useful in drug delivery and tissue engineering. Silk nanocomposites possess antioxidant and antimicrobial properties, which help in wound healing and cancer therapy. The following chapter highlights the recent advances in the synthesis of silk nanocomposites and their applications. It discusses the challenges of silk nanocomposites regarding their robustness, stability, suitability, and need for exploring the material for wider applications.