Abstract: With the intensifying challenges in energy, healthcare, natural resources and advanced materials, there is a growing need for new materials that combine high performance, biosafety and renewability. Silk fibroin, derived from natural silk, is readily processable, exhibits excellent mechanical properties and good biocompatibility, and offers controllable degradability. It shows great potential in biomedicine, smart wearables and flexible sensing. This review summarizes recent advances in the functionalization and creation of intelligent silk fibroin-based materials. Drawing on our group’s findings, it highlights progress in silk fibroin-based fibers, films, 3D constructs, biomedical scaffolds, self-powered devices and memristors. This review aims to guide the design and fabrication of high-performance, multifunctional and intelligent silk-fibroin materials.