This review article discusses the latest research on the production and application of spider silk and silk-based materials in biomedical and tissue engineering, with a focus on musculoskeletal tissues, skin regeneration, and tissue repair. Spider silk is highlighted as a natural, sustainable, and biocompatible material with excellent mechanical properties, making it a promising candidate for various medical applications. The article reviews the natural synthesis of spider silk, the recombinant production of spider silk proteins, and the development of different structures such as fibers, coatings, and 3D constructs for use in smart medical implants and drug delivery systems. It also explores the potential of spider silk in tissue engineering, including bone and cartilage repair, vascularization, ligament repair, muscle tissue regeneration, and peripheral nerve repair. The article emphasizes the advantages of spider silk, such as its high strength, biocompatibility, and ability to support tissue growth, while also acknowledging the challenges that remain, such as the need for further research and clinical trials. The review concludes with a discussion of spider silk's potential in nanomedicine and drug delivery systems, highlighting its role in targeted drug delivery and the development of novel biomaterials. Overall, the article presents a comprehensive overview of the current state of research on spider silk and its potential to revolutionize biomedical and tissue engineering applications.This review article discusses the latest research on the production and application of spider silk and silk-based materials in biomedical and tissue engineering, with a focus on musculoskeletal tissues, skin regeneration, and tissue repair. Spider silk is highlighted as a natural, sustainable, and biocompatible material with excellent mechanical properties, making it a promising candidate for various medical applications. The article reviews the natural synthesis of spider silk, the recombinant production of spider silk proteins, and the development of different structures such as fibers, coatings, and 3D constructs for use in smart medical implants and drug delivery systems. It also explores the potential of spider silk in tissue engineering, including bone and cartilage repair, vascularization, ligament repair, muscle tissue regeneration, and peripheral nerve repair. The article emphasizes the advantages of spider silk, such as its high strength, biocompatibility, and ability to support tissue growth, while also acknowledging the challenges that remain, such as the need for further research and clinical trials. The review concludes with a discussion of spider silk's potential in nanomedicine and drug delivery systems, highlighting its role in targeted drug delivery and the development of novel biomaterials. Overall, the article presents a comprehensive overview of the current state of research on spider silk and its potential to revolutionize biomedical and tissue engineering applications.