Therapeutic role of Nigella sativa (NS) seed oil fractions, methanolic extract (ME) and volatile oil (VO) and their constituents, thymoquinone (TQ) and limonene (LMN) in relation to lipidemic-oxidative stress in Wistar rats was determined. The total phenolic contents of NS seed oil and their ME and VO extracts were 320.00 ± 3.00, 300.12 ± 0.04 and 288.41 ± 0.01 mg gallic acid equivalents per 100 g of NS oil, respectively. Their Fe+2 chelating activities were 870.00 ± 2.00, 222.31 ± 5.80 and 38.59 ± 1.43 mg EDTA equivalents per 100 g of NS oil, respectively. These fractions and compounds exhibited strong antioxidant activities against 2,2-diphenyl-1-picryl hydrazyl, 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid, nitric oxide and hydroxyl radicals. Potential antiperoxidative effects of these fractions and compounds were also observed in liposome, and lipidemic-induced lipid peroxidation in atherogenic suspension fed rats, pretreated with 100 mg ME, 20 mg VO, 10 mg pure TQ or 200 mg LMN for 30 days. ME containing ω-6 linoleic acid and palmitic acid natural compounds was highly effective against lipidemic oxidative stress than VO extract possessing thymol and isothymol phenolic natural antioxidant compounds. TQ, principal compound shared to both the extracts. The test fractions and compounds effectively reduced the erythrocyte and liver lipid peroxidation markers, conjugated diene, lipid hydroperoxide and malondialdehyde to near normal levels in the order ME > TQ > VO > LMN, by directly counteracting free radicals as well as suppressing hepatic HMG-CoA reductase activity. Our findings demonstrated that these natural products, preferably ME possess significant antioxidant activities, and may be recommended as new potential sources of natural antioxidants.