The liver is a metabolically active organ which is prone to oxidative damage. The hepatoprotective effect of Nigella sativa (black seed oil extract) on carbon tetrachloride (CCl 4 )-induced hepatotoxicity in Sprague-Dawley albino rats was determined.There were four groups of eight rats; Group 1 (control) was administered with distilled water for 28 days, Group 2 was administered with 4 ml/kg of CCl 4 (70% olive oil: 30% CCl 4 ) on alternate days for 28 days. Group 3 was administered with 4 ml/kg of CCl 4 (70% olive oil: 30% CCl 4 ) and 2 ml/kg of Nigella sativa oil orally for 28 days.Group 4 was administered with 4 ml/kg of CCl 4 (70% Olive oil: 30% CCl 4 ) and 4 ml/kg of Nigella sativa oil orally for 28 days. Blood samples were collected for biochemical assessment. Liver, kidney, and brain tissues were determined for antioxidant enzymes and histopathological features. There were significant ameliorative effects of the oil extract in the treatment groups compared to control (p < .05). Practical applicationsNigella sativa (black seed oil) also known as Habbatus sauda has been used for therapeutic and nutritional purposes for decades due to its antioxidant, anti-inflammatory, and antitumor activities. It is a potent brain tonic due to the presence of linoleic, palmitic, oleic, eicosapentanoic (EPA), and docosahexaenoic acids (DHA), hence, may enhance brain and heart functions. This research analysis carried out on the neurotransmitter (glutamate and GABA) levels showed a significant decrease at p < .05 in the group administered with CCl 4 alone, which was reversed significantly upon the administration of Nigella sativa oil. The histological features reported in the current study correlated with the biochemical parameters. The CCl 4 induced severe histological changes on the hepatic, renal, and brain tissues, which, was ameliorated by the Nigella sativa oil administration. The administration of Nigella sativa oil exerted a protective effect on the brain, liver, and kidney during CCl 4 -induced oxidative stress. K E Y W O R D Scarbon tetrachloride, hepatotoxicity, neuroprotection, neurotransmitter, Nigella sativa (black seed oil), oxidative stress, γ-aminobutyric acid (GABA) ple to give a decrease in absorbance of about 0.02 abs/min, and the reaction was started by 5.0 μmol H 2 O 2. The same full reaction in the presence of 1.0 μmol sodium azide was the blank. Azide will completely inhibit catalase.