Nigella sativa L. (Ranunculaceae) is considered as a therapeutic plant-based medicine for liver damage. In this study, the aim was to study the effect of Nigella sativa oil (NSO) pretreatment on ethanol-induced hepatotoxicity in rats. Rats were given Nigella sativa oil at doses of 2.5 and 5.0 mL·kg −1 , orally for 3 weeks, followed by oral ethanol (EtOH) administration (5 g·kg −1 ) every 12 h three times (binge model). Binge ethanol application caused significant increases in plasma transaminase activities and hepatic triglyceride and malondialdehyde (MDA) levels. It decreased hepatic glutathione (GSH) levels, but did not change vitamins E and vitamin C levels and antioxidant enzyme activities. NSO (5.0 mL·kg −1 ) pretreatment significantly decreased plasma transaminase activities, hepatic MDA, and triglyceride levels together with amelioration in hepatic histopathological findings. NSO pretreatment may be effective in protecting oxidative stress-induced hepatotoxicity after ethanol administration