Electroformed giant unilamellar vesicles (GUVs) were found to have optimal sizes (~10 µm average diameter) for studying effects of photosensitizers and antioxidants in lipid bilayers as food models. By using optical microscopy and digital image processing techniques, no membrane damage was found for hydrophilic riboflavin, while lipophilic chlorophyll a initiated GUV budding and subsequent disintegration under light irradiation, indicating that lipophilic photosensitizers are the more important in such structured lipids. Lipophilic β-carotene provided protection against oxidative damage induced by chlorophyll a as shown by an increased lag phase for budding; however, it had no effect on subsequent budding rate. Hydrophilic puerarin alone exhibited little protection in terms of lag phase, but decreased together with β-carotene budding rate after the lag phase by a factor of more than 2, showing a clear synergistic effect between a hydrophilic antioxidant, inactive in the aqueous phase alone, and a lipophilic antioxidant protecting lipids.