The present study aimed to modulate the photoreactivity of bufexamac, with a focus on photostability and phototoxicity, by forming an inclusion complex with sulfobutylether-β-cyclodextrin (SBECD). The photobiochemical properties of bufexamac were evaluated by reactive oxygen species (ROS) assay and using in vitro photogenotoxic assessment tools. To assess the inclusion properties of SBECD complex with bufexamac, a UV absorption spectroscopic study was also carried out. The influence of SBECD on the photoreactivity of bufexamac was analyzed by ROS assay and photostability test. From the photobiochemical data, superoxide generation from irradiated bufexamac indicated its photoreactivity; however, the photogenotoxic risk of bufexamac was negligible owing to low DNA-binding affinity and DNA-photocleaving activity. SBECD complex of bufexamac was formed, and the association constant of the complex was calculated to be 620M(-1). On the basis of the photochemical data on bufexamac co-existing with SBECD, ROS generation from irradiated bufexamac (200μM) was inhibited by SBECD at concentrations of over 20μM. The degradation constant of bufexamac in SBECD was decreased ca. 30% compared with that of bufexamac, suggesting improvement of its photostability. The phototoxic risk of bufexamac might be attenuated by SBECD complexation, and cyclodextrin inclusion complexes might be a useful approach for modulating the phototoxicity of drugs.