Musculoskeletal engineering has been considered as a promising approach to customize regenerated tissue (such as bone, cartilage, tendon, and ligament) via a self-healing performance. Recent advances have demonstrated the great potential of bioactive materials for regenerative medicine. Silk fibroin (SF), a natural polymer, is regarded as a remarkable bioactive material for musculoskeletal engineering thanks to its biocompatibility, biodegradability, and tunability. To improve tissue-engineering performance, silk fibroin is hybridized with other biomaterials to form silk-fibroin-based hybrid biomaterials, which achieve superior mechanical and biological performance. Herein, we summarize the recent development of silk-based hybrid biomaterials in musculoskeletal tissue with reasonable generalization and classification, mainly including silk fibroin-based inorganic and organic hybrid biomaterials. The applied inorganics are composed of calcium phosphate, graphene oxide, titanium dioxide, silica, and bioactive glass, while the polymers include polycaprolactone, collagen (or gelatin), chitosan, cellulose, and alginate. This article mainly focuses on the physical and biological performances both and study of several common silk-based hybrid biomaterials in musculoskeletal engineering. The timely summary and highlight of silk-fibroin-based hybrid biomaterials will provide a research perspective to promote the further improvement and development of silk fibroin hybrid biomaterials for improved musculoskeletal engineering.