Silk fibroin (SF) is a promising biomaterial in regenerative medicine due to its enhanced bio/cytocompatibility, chemical stability, and mechanical properties. SF can be produced from silkworm cocoons and processed into various forms, including films, fibers, hydrogels, 3D scaffolds, and particles. These materials are versatile and can be tailored for diverse biomedical applications, such as bone, cartilage, cardiovascular, neural, skin, and pancreatic tissue regeneration. SF-based materials are produced from an aqueous solution through degumming, dissolution, and regeneration techniques. The structural and functional properties of SF are influenced by its composition, which includes fibroin and sericin, and its ability to form different conformational states, such as Silk I and Silk II. SF-based composites, such as SF/SR and SF with other biopolymers, have been developed to enhance mechanical and biological properties. SF-based materials exhibit good biocompatibility, with studies showing minimal inflammatory responses and no significant allergenicity. However, some studies suggest that SF-SR composites may trigger immune responses, requiring further investigation. Overall, SF-based materials are promising for biomedical applications due to their tunable properties, biocompatibility, and potential for long-term use in tissue engineering and regenerative medicine.Silk fibroin (SF) is a promising biomaterial in regenerative medicine due to its enhanced bio/cytocompatibility, chemical stability, and mechanical properties. SF can be produced from silkworm cocoons and processed into various forms, including films, fibers, hydrogels, 3D scaffolds, and particles. These materials are versatile and can be tailored for diverse biomedical applications, such as bone, cartilage, cardiovascular, neural, skin, and pancreatic tissue regeneration. SF-based materials are produced from an aqueous solution through degumming, dissolution, and regeneration techniques. The structural and functional properties of SF are influenced by its composition, which includes fibroin and sericin, and its ability to form different conformational states, such as Silk I and Silk II. SF-based composites, such as SF/SR and SF with other biopolymers, have been developed to enhance mechanical and biological properties. SF-based materials exhibit good biocompatibility, with studies showing minimal inflammatory responses and no significant allergenicity. However, some studies suggest that SF-SR composites may trigger immune responses, requiring further investigation. Overall, SF-based materials are promising for biomedical applications due to their tunable properties, biocompatibility, and potential for long-term use in tissue engineering and regenerative medicine.