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 center dot). 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.