Silk, renowned for its versatility, encompasses a diverse array of applications spanning from textiles to biomedical and industrial realms. The attributes of silk, namely its biocompatibility, sustainability, mechanical robustness, and stimuli-responsiveness, make it a highly attractive option for various smart material applications. The stimuli-responsive behavior of silk can be explained by its structural architecture and composition, where hydrogen bonds in β-sheet zones and the amorphous area function as switch and net points, respectively. The sensitivity to water reminds of typical shape memory properties of spider silk, where it can super-contract by approximately 50% when immersed in water, and also the motion caused by the interaction of water molecules and fibroin chains increased the stiffness of the actuator film by about 13%. Herein, diverse stimuli-responsive systems of silk, including doxorubicin-grafted silk fibroin (SF) particles, polyvinyl alcohol (PVA)/ silk hybrids, and a composite comprising graphene, SF, and calcium ions (Gr/SF/Ca2+) are being discussed in this paper. The feasibility of advancing biomedical device development, including patient-specific injectable scaffolds for applications in tissue engineering, wound healing, drug delivery, and actuators, has been comprehensively addressed here.