Arbidol, a broad and potent antiviral molecule, incorporates rapidly into membranes. To gain further insight into the mode of action of Arbidol, since the exact antiviral mechanism of Arbidol is unknown, I examined its interaction and effects on model membranes composed of saturated phospholipids by performing a detailed biophysical study using calorimetry and infrared spectroscopy. Arbidol interacts and modifies the physicochemical properties of the phospholipids in the membrane, having a significant effect on negatively charged phospholipids but a minor one on zwitterionic phospholipids. The data suggest that Arbidol is located at the interface of the membrane, participates in hydrogen bonding either with water or the phospholipid or both, and decreases the hydrogen bonding network of the phospholipids giving place to a phospholipid phase similar to the dehydrated solid one. The significant effects produced on negatively charged phospholipids suggest that the active molecule of Arbidol in the membrane is the protonated one, that is, the positively charged molecule. These data suggest that the potent antiviral effects of Arbidol are mediated at least in part through its membranotropic effects, likely giving place to the formation of perturbed membrane structures. These modifications interfere with proper membrane functioning and should be responsible for its broad antiviral activity.