This investigation set out to evaluate the effects of omega-3 on biochemical and histological indicators in white rats subjected to phenobarbital-induced oxidative stress. The research was carried out on adult male rats at the physiology lab at the College of Veterinary Medicine at Al-Qadisiya University between June and December of 2022. Forty adult male Wistar rats (aged 90 days and weighing 150±10 g) were randomly divided into four groups. The control group (C) received water drench treatment for 30 days, the Omega-3, group (S) received 30 mg/ kg b.w., the phenobarbital group (S) received 80 mg/kg b.w., and the Omega-3, and phenobarbital group (S) received both treatments for 30 days. Males were anesthetized (by injection of 0.3 ml ketamine + 0.1 ml of xylazine/ kg b.w. ip), dissected, and blood samples were taken from the abdominal vein in non-heparinized tubes at the conclusion of each treatment and control subgroup period. Liver enzymes (AST, ALT, and ALP), kidney function (Urea and Creatinine), and lipid profile (Cholesterol, Triglyceride, HDL, and LDL) were measured by analyzing blood serum samples. From each rat has had a liver and kidney removed for histological analysis. Serum liver enzymes were found to have significantly increased in the omega-3, group and decreased in the phenobarbital group after each trial period. Serum levels of liver enzymes decreased in the omega-3, group while increasing in the phenobarbital group. Serum lipid profiles also showed notable changes: a drop in the omega-3, group and an increase in the phenobarbital group. The inspection of the group given 80 mg/ kg of phenobarbital revealed severe degeneration and necrosis of hepatocytes, as well as a loss of the radial organization of the cells around the major vein, indicating the presence of a massive thrombose in the hepatic tissue. Examination of the livers of the T3 group treated with Omega-3, at a concentration of 30 mg/ kg revealed normal liver tissue in which the hepatocytes appeared arranged in a hexagonal radial shape around the central vein, the bile duct appeared normal, and there was no loss of hepatocytes around congestive areas, even at higher magnification. The hepatocytes looked fine, too. The results showed that minimal vaculation and no loss of hepatocord occurred in the T4 group given 80 mg/ kg B.W. of phenobarbital in combination with 30 mg/ kg B.W. of Omega-3,. The liver's normal tissue, with its hepatocytes grouped in a hexagonal radial pattern around the central vein and its bile duct appearing unaffected, was also visible, indicating the absence of hepatic degeneration and significant damage. A considerable atrophy of glomeruli, severe necrosis and degeneration in the epithelial line of renal convoluted tubules, and dilatation in lumen of these tubules were seen in the histological section obtained from a rat given a dosage of phenobarbital (80 mg/ kg b.w.). In contrast, microscopic examination revealed obvious glomerular atrophy alongside necrosis in the epithelial cells that border the renal convoluted tubules and bleeding throughout the renal tissues. Normal, proliferating glomeruli lined by endothelial cells and normal, convoluted tubules lined by epithelial cells were found in this histological region of the kidney. The results showed modest necrosis in all renal tissues and mild bleeding in the mix group given 80 mg/kg B.W. of phenobarbital and 30 mg/ kg B.W. of Omega-3, Normal renal convoluted tubules lined by epithelial cells, and normal proliferating glomeruli lined by endothelial cells. We conclude that Omega-3, fatty acid antioxidant activity has pharmacological benefit in normal intact male rats in the absence of oxidative stress, both as an antioxidant and as an inducer of endogenous enzymatic and non-enzymatic antioxidants.