Biological membranes are composed of a lipid bilayer with a heterogeneous structure and complex dynamics, both of which can be modulated by the presence of melatonin. The lateral heterogeneities in lipid bilayers, also known as lipid rafts, have unique molecular interactions with melatonin, which we review here. Specifically, we discuss the molecular-level, physicochemical influences of melatonin on dynamics of lipid rafts and their structural properties, including melatonin’s propensity to preserve the structural integrity of lipid rafts at different length scales, as revealed through a range of experimental techniques and theoretical approaches.