Abstract Models of amphiphilic NO‐donor antioxidants 24 – 26 were designed and synthesized. The products were obtained by linking a lipophilic tail (C 6 , C 8 , C 10 ) with a polar head constituted by the 2,6‐dimethoxyphenol antioxidant joined to the NO‐donor 3‐furoxancarboxamide substructure through a bridge containing a quaternary ammonium group. Compound 23 , containing the shortest C 2 ‐alkyl chain, was also studied as a reference. The antioxidant properties (TBARS and LDL oxidation assays) and the vasodilator properties of the compounds were studied in vitro. The ability of these products to interact with phospholipid vesicles was also investigated by NMR techniques. The results indicate that both activities are modulated by the ability of the compounds to accumulate on phospholipid layers.