Moringa oleifera gained importance as a medicinal plant. The current study assesses Moringa leaf ethanol extracts (MLE) against experimentally diclofenac sodium (DcNa) ‐induced liver toxicity in male rats. Leaves were extracted with different solvents differing in polarity. Assessment involved total phenolic compounds, total flavonoids and radical scavenging activity against 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH•). HPLC was performed for identifying phenolic compounds, wherein ethyl vanillin (1,205 mg/kg), 3‐OH‐tyrosol (812.2 mg/kg), benzoic acid (273.8 mg/kg), salicylic acid (240.0 mg/kg), chlorogenic acid (233.3 mg/kg) and 3,4,5‐methoxy‐cinnamic acid (172.5 mg/kg) were measured. Fifty animals (each treatment group consisted of 10 rats) were subjected to five treatments and the experiment lasted for 4 weeks. Animals were exposed to DcNa (100 mg/kg) and two doses of MLE as well as silymarin (an antioxidant flavonoid C25H22O10) for 4 weeks. Liver marker enzymes, including alkaline phosphatase, alanine transaminase, and aspartate transaminase as well as urea, uric acid, and creatinine were increased. Serum albumin and total protein decreased in DcNa‐treated rats. Homogenates nitric oxide increased in liver tissue of the DcNa‐treated rats, while the activity of each of glutathione peroxidase, glutathione‐S‐transferase, glutathione, and catalase decreased. It could be concluded that MLE in both doses and silymarin are considerably hepatoprotective with antioxidant activity (AOA) against DcNa‐induced hepatotoxicity in rats.