Moringa oleifera (MO) is a common herbal plant used as human food and for medicinal purposes worldwide. Acetaminophen (APAP) is used as antipyretic and analgesic drug, while causing hepatotoxicity at over dose.The present study is aimed to evaluate the hepatoprotective effect of MO seed oil extract against the biochemical changes induced by APAP in male adult albino rats. Thirty five male albino rats were used in this study, divided randomly into five groups (7 rats in each). The 1^st control group; untreated animals, the 2^nd saline group received single dose of normal physiological saline, the 3 ^rd group treated with single dose of APAP (500 mg / kg b.wt) for hepatotoxicity induction, the 4^th group treated with MO seed oil extract (0.3 ml/rat) daily for 30 days and the 5^th group treated with a single dose of APAP and with MO seed oil extract daily for 30 days to evaluate its protective effects. Blood samples were collected for serum preparation and biochemical analysis. Results showed that APAP induced a significant increase in blood glucose level which is against to the effect produced by the treatment with MO seed oil. All measured kidney function parameters increased significantly after treatment with APAP. Oppositely, animals treated with MO seed oil after APAP showed depression in kidney function parameters. APAP treated group showed significant decreases in catalase (CAT) activity and reduced glutathione (GSH) level while showed a significant increase in malondialdehyde (MDA) activity. Rats treated with MO seed oil showed significant increases in catalase and GSH activities while caused a significant decrease in MDA concentration. Treatment with MO seed oil after APAP induced significant decrease and increase in GSH and MDA levels respectively compared to those of control group. The present study concluded that the MO seed oil extract has ameliorative effects against some biochemical disturbances induced by acetaminophen possibly through its anti-oxidative properties.