Alcohol addiction elicits oxidative imbalance and it is well known that polyphenols possess antioxidant properties. We investigated whether or not polyphenols could confer a protective potential against alcohol-induced oxidative stress.We administered (per os) for two months 20 mg/kg of olive polyphenols containing mostly hydroxytyrosol in alcoholic adult male mice. Hydroxytyrosol metabolites as hydroxytyrosol sulfate 1 and hydroxytyrosol sulfate 2 were found in the serum of mice administered with polyphenols with the highest amount in animals treated with both polyphenols and alcohol. Oxidative stress was evaluated by FORT (free oxygen radical test) and FORD (free oxygen radical defense) tests.Alcoholic mice showed a worse oxidative status than nonalcoholic mice (higher FORT and lower FORD) but polyphenol supplementation partially counteracted the alcohol pro-oxidant effects, as evidenced by FORT.A better understanding of the antioxidant protection provided by polyphenols might be of primary interest for drug discovery and dietary-based prevention of the damage associated with chronic alcohol abuse.