SummaryBackground Aims Red wine polyphenols inhibit chemically-induced oxidative DNA damage in vivo in experimental animals through a mechanism which is still unclear. On this basis, we tried to clarify the mechanisms of inhibition of DNA oxidation in vitro by wine extracts containing monomeric and polymeric phenols (WE) and monomer-free complex polyphenols and tannins (WCPT) from red wine. Methods Oxidative DNA damage was induced by incubating DNA with GSH/Fe3+ or cumene hydroperoxide (CumOOH) in vitro and using 8-OH2-deoxyguanosine (8-OHdG) levels as a measure of DNA oxidation. Levels of 8-OHdG were determined by HPLC coupled with electrochemical detector (ESA). Results and conclusions WCPT and WE, at M concentrations, reduced concentration-dependently oxidative DNA damage induced by GSH/Fe3+. WCPT and WE also reduced DNA oxidation by CumOOH. In conclusion, complex polyphenols and tannin extracts from red wine, with or without small molecular phenols, prevent oxidative DNA damage through a dual mechanism, iron binding and direct free radical scavenging.