AbstractStimuli‐responsive hydrogels are essential for the future development of synthetic materials that could exchange information with living tissues. In this Article, we present the synthesis of biocompatible hydrogels with an unprecedented range of photocontrolled rigidity. The hydrogels are based on dual physical and chemical crosslinking. Chemical crosslinks are the result of thiol maleimide Michael addition; physical crosslinks are based on host–guest interactions between azobenzene and β‐cyclodextrin moieties. The final properties of the materials are tuned by a design‐of‐experiment approach. This strategy enables us to obtain a hydrogel with mechanical properties close to routinely used agarose gel while maintaining a low UV‐visible absorption. The Young's modulus is monitored in real time during AFM nanoindentation experiments under irradiation. Upon UV and visible irradiation cycles, the hydrogel exhibits a range of reversible evolution greater than 30 %, which is also associated with cycles of swelling/shrinking. A biocompatible hydrogel with predictable and phototunable stiffness and a high variation in mechanical properties has thus been obtained for the first time.