The aims of our study were the evaluation of the hepatoprotective effect and antioxidant role of walnuts against ethanol-induced oxidative stress. The hepatoprotective and antioxidant role of the walnuts supplementation feed against ethanol-induced oxidative stress were evaluated by measuring liver damage serum marker enzymes; aspartate aminotransferase (AST); alanine aminotransferase (ALT); gamma glutamyl transpeptidase (GGT); lactate dehydrogenase (LDH); and antioxidant defense systems such as reduced glutathione, glutathione reductase, superoxide dismutase, glutathione-S-transferase, catalase, and glutathione peroxidase and Malondialdehyde (MDA) content in various tissues of rats. Rats were divided into six experimental groups: I (control), II (20 % ethanol), III (10 % walnuts), IV (20 % ethanol + 10 % walnuts), V (5 % walnuts), and VI (20 % ethanol + 5 % walnuts). According to the results, the biochemical analysis showed a considerable increase in the serum aspartate AST, ALT, GGT, and LDH in the group II as compared to that of group I, whereas decreased in group IVas compared to that of group II. In addition, administration of walnuts supplementation restored the ethanol-induced imbalance between MDA and fluctuated antioxidant system toward close control group particularly in the tissues. The results indicated that walnuts could be as important as diet-derived antioxidants in preventing oxidative damage in the tissues by reducing the lipid oxidation or inhibiting the production of ethanol-induced free radicals in rats.