Ethanol consumption may be deleterious to the liver. However, alcoholic beverages contain, besides ethanol (EtOH), complex chemical mixtures that can modify EtOH's adverse effects. Red wine (RW) is rich in polyphenolic antioxidants, often reported as hepatoprotective agents. This study aimed to investigate the effects of 6 months of RW ingestion on hepatic oxidative stress and inflammation. Six-month-old Wistar rats were treated with RW or EtOH; controls were pair-fed. EtOH increased 8-hydroxy-2'-deoxyguanosine and decreased reduced and oxidized glutathione. These animals also displayed stimulated superoxide dismutase, catalase, and glutathione reductase activities. RW treatment decreased malondialdehyde and reduced glutathione levels. Glutathione-S-transferase and selenium-dependent glutathione peroxidase activities were stimulated and glutathione reductase activity was inhibited by RW intake. No modifications were detected in nuclear factor-kappa B or alkaline phosphatase activities. EtOH consumption induced fibrosis in portal spaces and hepatocyte lipid accumulation that were absent with RW treatment. This paper highlights the importance of RW nonalcoholic components and the relevance of biological matrix in the study of EtOH oxidative effects.