Luteolin (LT), a flavonoid known for its health benefits was investigated for possible ameliorative effects against hepato-renal toxicity induced by diethylnitrosamine and carbon tetrachloride in rats. Thirty-six male Wistar rats were assigned into six groups; One and two served as control and intoxicated groups, groups three-five were intoxicated and treated with LT at 10, 20 and 40mg/kg, respectively and group six received LT only (20mg/kg). The LT was given orally three times a week while Diethylnitrosamine (DEN) (50mg/kg) and CCl4 (0.5mL/kg) were administered intraperitoneally once a week for four consecutive weeks. Toxicants exposure significantly increased the activities of serum aminotransferases (ALT and AST) by 28% and 30%, and levels of serum urea and creatinine by 15% and 28%, respectively. The intoxication increased lipid peroxidation by 81% and 25%, and also decreased superoxide dismutase by 16% and 17%, and reduced glutathione by 31% and 25% in the liver and kidney of rats, respectively. In addition, inflammatory markers, myeloperoxidase and nitric oxide increased in the liver by 650% and 49%, and in the kidney by 367% and 11%, respectively in the intoxicated rats. Histology of liver revealed necrosis and multifocal hepatocellular coagulation while glomerular atrophy and tubular epithelial necrosis were seen in kidneys of intoxicated rats. Interestingly, LT pretreatment significantly attenuated markers of oxidative stress and inflammation in the liver and kidney of intoxicated rats. In conclusion, luteolin may serve as chemotherapeutic agent to mitigate the adverse effects of chemicals on the hepato-renal tissues of animals.