Investigating the AChE/MAO-B dual inhibitory activity of some newly synthesized donepezil-like 2-benzylideneindan-1-one derivatives, which differ for bulkiness/lipophilicity of the unconjugated tertiary amino head, we gathered new clues about the photoswitchable E/Z isomerization controlling inhibitors’ binding to two AD-related target enzymes. Here, ACHE is linked to Alzheimer disease.