Technical Abstract: Ferulic acid and its esters are known to be effective antioxidants. Feruloyl dioleoylglycerol was assessed for its ability to serve as an antioxidant in model membrane phospholipid vesicles. The molecule was incorporated into single-lamellar vesicles of 1,2-dioleoyl-sn-glycero-3-phosphocholine at one and five mole fraction. Employing a lipid peroxidation inhibition assay, feruloyl dioleoylglycerol was demonstrated to express an oxidation protection ratio relative to Trolox of 0.94 and 0.74 at the 1% and 5% incorporation levels, respectively. The impact of feruloyl dioleoylglycerol incorporation on vesicle integrity was examined by determining calcein—cobalt complex leakage rates. Vesicle leakage was not influenced at 22 or 37 deg C with 5% feruloyl dioleoylglycerol incorporation in comparison to vesicles lacking feruloyl dioleoylglycerol. Resonance energy transfer analysis showed that the closest approach distance between feruloyl dioleoylglycerol and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) was approximately 31 Å, which indicated that feruloyl dioleoylglycerol was thoroughly distributed throughout the bilayer plane. Conformational analysis determined that feruloyl dioleoylglycerol has a splayed conformation in which its feruloyl moiety is not closely contacted by its oleoyl groups. Feruloyl dioleoylglycerol integrates into the bilayer with its feruloyl moiety oriented close to the hydrophilic/lipophilic interface and its oleoyl groups extended deeply in the membrane. These findings indicate feruloyl dioleoylglycerol expresses antioxidant activity by intercepting aqueous-phase free radicals as they penetrate the bilayer.