Introduction:Mercury chloride is commonly used in our daily lives due to its diverse applications and can induce hepatorenal toxicity even at low doses. The present investigation studies the preventive effects of lipoic acid and Cleome droserifolia extract against mercury induced hepatorenal toxicity. Methods: Thirty male albino rats were randomly assigned to six experimental groups. The f irst group served as the normal control. The second group was treated with alpha-lipoic acid (ALA) at a dose of 10 mg/kg. The third group received Cleome droserifolia extract (CD) at the same dose. The fourth group was exposed to mercuric chloride (HgCl2 ) at 35 mg/kg (equivalent to 21% of the LD50 ). The fifth group was co-treated with alpha-lipoic acid (10 mg/kg) and mercuric chloride (35 mg/kg), while the sixth group received Cleome droserifolia extract (10 mg/kg) together with mercuric chloride (35 mg/kg). All treatments were administered orally once daily for a period of eight weeks. Results: Mercury induced a slight decline in body weights and relative organ weights for the liver and kidney compared to the normal control group. It caused significant elevations (p<0.05) in hamoglobin concentration and white blood cell (WBC) count; however, bone marrow cell count was not affected. Mercury triggered considerable disruption in liver and kidney functions. It also promoted a significant decline in catalase (CAT) activity and a significant elevation in malondialdehyde (MDA) levels. Mercury-induced degeneration, f ibrosis, and necrosis in the liver and kidney tissues. Administration of alpha lipoic acid and Cleome droserifolia extract showed marked improvement in the different parameters under investigation. Conclusion: Lipoic acid was found to be more effective against mercury chloride-induced hepatorenal toxicity than Cleome droserifolia extract.