Development of hydrogel materials that respond to specific stimuli has been of significant interest in the design of modern functional materials. A variety of previous studies have used the ligand-binding capability of proteins to design hydrogels that change their crosslinking density in response to stimuli. However, these materials generally undergo relatively small dynamic response, with limited control over response characteristics. This manuscript describes an alternative approach that exploits the ability of proteins to undergo nanometer-scale conformational changes in response to stimuli. We report a class of novel protein-based hydrogel materials that undergo tunable, reversible dynamic responses with a wide dynamic range (volume decreases to ∼25–90% of initial volume). These materials also undergo tunable, reversible changes in optical transparency (optical transparency decreases to ∼35–100% of initial optical transparency), and this phenomenon is used as a mechanism for label-free biosensing. The materials are generated by photo-crosslinking of an engineered version of the protein calmodulin flanked on each end with poly(ethylene glycol)-diacrylate (PEGDA) moieties. The mechanism for dynamic changes derives from calmodulin's well-characterized “hinge motion”-upon-ligand binding. Variations in network parameters in these hydrogels, including the molecular weight between cross-links and the cross-linking density, result in systematic tuning of material responsiveness. The influence of network parameters on hydrogel dynamics reported here may serve as a guide for the design of other protein-based, responsive materials assembled using similar principles, and these materials may be a useful platform for design of biosensors, actuators, and drug delivery systems.