Significance: The majority of deformable actuators rely on synthetic materials with stimuli-responsive properties to execute the system, limiting their use in vivo. We designed and built a new class of bionic actuator entirely out of biocompatible and biodegradable materials. Stimuli-responsive genetically engineered silk–elastin-like proteins (SELPs) and cellulose nanofibers (CNFs) are combined to fabricate an actuator system that could effectively respond to physical and chemical stimuli. Programmable and reversible deformations in response to the stimuli have been achieved with this actuator. The SELP/CNF actuator provides an option for fields such as in vivo biomedical soft robotics and biomimetic devices where biocompatibility, biodegradability, biomedical signals recognition, and durability are desired.