Carbon tetrachloride (CCl4) causes severe injury to the body particularly the liver and the kidney. The aim of the present study was testing the probable hepatonephro protective effect of Moringa oleifera seed methanolic extract against CCl4 toxicity in male rat. 24 male rats were divided into 4 groups (n=6); the first group (G1) was the negative control group, rats of the other three groups were injected with CCl4 twice a week. Rats of the second group (G2) were kept without treatment as positive CCl4 group, the third group (G3) received a daily dose of M. oleifera methanolic extract and the fourth group (G4) received a silymarin dose as a positive treated group. The HPLC analysis of M. oleifera seed methanolic extract revealed that it is rich in ascorbic and oleic acids. Rats of the CCl4 positive control group showed an increase in kidney and liver injury markers, interleukin-6, bilirubin and lipid peroxidation, and a decrease in antioxidants activity and total protein. In addition, liver and kidney tissues showed drastic histopathological changes. Treating the CCl4 hepatonephrotoxicity in G3 and G4 with either M. oleifera seed methanolic extract or silymarin, respectively significantly alleviated all altered biochemical and histological changes approaching the normal values. M. oleifera methanolic extract revealed more protection to liver and kidney in G3 than silymarin in G4. This protecting activity of M. oleifera seed methanolic extract against CCl4 hepatonephrotoxicity may be ascribed to its high content of phenols and flavonoids, in addition to ascorbic acid and oleic acid.