F1Fo-ATP synthase is one of the best studied macromolecular machines in nature. It can be inhibited by a range of small molecules, which include the polyphenols resveratrol and piceatannol. Here, we introduce Photoswitchable Inhibitors of ATP Synthase, termed PIAS, which were synthetically derived from these polyphenols. They can be used to reversibly control the enzymatic activity of purified yeast Yarrowia lipolytica ATP synthase by light. Our experiments indicate that the PIAS described here bind to the same site in the ATP synthase F1 complex as the polyphenols in their trans form but they do not bind in their cis form. The new PIAS compounds could be useful tools for the optical precision control of ATP synthase in a variety of biochemical and biotechnological applications.