The development of highly effective systems for drug delivery is crucial in biomedical care. Protein-based carriers have gained more importance in drug delivery as they are more advantageous than conventional drug delivery systems. Silk fibroin is a naturally occurring protein derived from cocoons of Bombyx mori. It has high potential in biomedical fields for its excellent biocompatibility and biodegradability. Due to its unique properties, it is highly capable of loading and delivering various biomolecules, drugs and other moieties as therapeutics. Many emphases have been directed to develop SF-based nano-drug delivery for its strong binding capacity for a wide range of drugs, controlled drug release characteristics, and ease of fabrication. The recent developments on SF-based nanoparticles have been highlighted in this review, covering SF’s chemical structure, properties and preparation methods. Also, recent functions of SF for the fabrication of nano-drug delivery systems are discussed.