Polyphenolic compounds have been implicated as the active ingredients for the cardiac protective effect in red wine. We tested the effects of dietary supplementation of polyphenols from grape (GP) and chronic ethanol administration on low-density-lipoprotein (LDL) oxidation and platelet function in rats. Four groups of young male Sprague-Dawley rats were fed the following diets for 2 months: (I) a high fat Lieber-DeCarli liquid diet with an isocaloric amount of maltose, (II) with 5% ethanol (w/v), (III) with 5 mg/dL of GP, and (IV) ethanol plus GP. Platelet aggregation was induced by thrombin and phorbol myristate acetate (PMA) and LDL oxidation was induced by Cu2+. Chronic ethanol administration resulted in a significant increase in LDL oxidation and this effect was partially protected by supplementation with GP. Although platelet number was not affected by either ethanol or GP administration, platelet aggregation induced by thrombin was reduced in ethanol, GP and ethanol plus GP groups as compared to controls. On the other hand, platelet aggregation induced by PMA was not altered in any groups, suggesting that protein kinase C was not a causal factor for the reduction of aggregatory response induced by thrombin. These results show similar effects of ethanol and GP on platelet aggregation but different effects on LDL oxidation. It can be concluded that dietary supplementation with GP may exert partial protection on oxidative insults such as those elicited by chronic ethanol ingestion.