Propolis is a resinous compound made by bees with well-known biological activity. However, comparisons between encapsulated and non-encapsulated propolis are lacking. Therefore, the antibacterial activity, effect on the phase transition of lipids, and inhibition of UV-induced lipid oxidation of the two forms of propolis were compared. The results showed that non-encapsulated propolis produces quicker effects, thus being better suited when more immediate effects are required (e.g., antibacterial activity). In order to gain an in-depth introspective on these effects, we further studied the synergistic effect of propolis compounds on the integrity of lipid membranes. The knowledge of component synergism is important for the understanding of effective propolis pathways and for the perspective of modes of action of synergism between different polyphenols in various extracts. Thus, five representative molecules, all previously isolated from propolis (chrysin, quercetin, trans-ferulic acid, caffeic acid, (-)-epigallocatechin-3-gallate) were mixed, and their synergistic effects on lipid bilayers were investigated, mainly using DSC. The results showed that some compounds (quercetin, chrysin) exhibit synergism, whereas others (caffeic acid, t-ferulic acid) do not show any such effects. The results also showed that the synergistic effects of mixtures composed from several different compounds are extremely complex to study, and that their prediction requires further modeling approaches.