In the present contribution, we have shown that biomimetic cyclocurcumin analogous, showing enhanced photophysical properties and in particular E/Z photoisomerization, may be internalized in model lipid membranes, providing that hydrophobic alkyl chains are appended to the photo-active core. The results of enhanced sampling MD simulations have shown that the two isomers present a different FEP for the interaction with the membrane. Indeed, while the E-isomer will form a stable aggregate located at the lipid core/polar head interface, the Z counterpart leads to a metastable interaction with the membrane. Thus, we have synthetized the butyl-appended CyP-OBu and confirmed its ideal photoisomerization capacities, i.e. fast, reversible and fully lightcontrolled E/Z and Z/E photoisomerization with high resistance to fatigue. We have also shown that both isomers do interact with liposomes and monolayers DPPC films, albeit with different characteristic. Anyway, a concentration-dependent fluidification of the membrane is observed, and the properties of the lipid layers are modified following irradiation under UV light suggesting the possible use of the photo-switch for therapeutic purposes. Interestingly, both experimental results and molecular modeling suggests that the slow release of the Z-isomer is also in competition with a much faster structural reorganization inside the membrane, thus leading to a complex time evolution.