Specific protein-cell and drug-cell interactions have been widely used to manipulate stem cell fate. Despite extensive studies, most current platforms cannot realize reversible manipulation of stem cell differentiation. In this work, we report a photodynamic zwitterionic hydrogel capable of reversibly triggering and suspending the differentiation process via manipulating nonspecific interactions between cultured stem cells and the hydrogel. The differentiation state of stem cells can be altered by exposing the hydrogel to a selected light program, while differentiation can be immediately suspended when near-infrared exposure converts the hydrogel into a purely zwitterionic form. While many other studies apply specific interactions to control stem cell fate, this work provides a completely different approach—allowing reversible, real-time and localized manipulation of stem cell fate choice via nonspecific interactions.