This research aimed to determine the antioxidant activity and protective effects of Nigella sativa seed extracts against liver and kidney injuries induced by oxytetracycline (OTC) in albino rats. Oil extract (NSO) was prepared by cold pressing that contains fixed and essential oil. Essential oil (EO) was also prepared by hydro-distillation; its contents were identified as twenty-six terpenoids. Ethanolic extract (NSET) was also prepared and its contents of phenols and flavonoids were quantified. Antioxidant activity of both NSO and NSET were measured using DPPH and ABTS. The protective effect of each of NSO and NSET against oxidative stress was determined in Albino rats. Results showed that the liver and kidney weight gain at the end of experiment were decreased in the both extracts while increased in the OTC-treated group. Enzymatic antioxidants, SOD, CAT, and G-px, showed a substantial inhibition in OTC-treated group compared with extract-treated groups. Liver function and kidney function parameters as well as malondialdehyde (MDA) level increased significantly in OTC-treated group while they decreased in extract-treated groups. The preventive properties of the extracts were validated in histological investigation of liver and kidney.