Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. The present study was designed to underline the protective mechanism of Nigella sativa (NS) and green tea (GT) against Fe-NTA-induced renal damage. Fe-NTA (5 mg Fe/kg body weight, i.p.) enhanced serum urea and creatinine levels, lactate dehydrogenase and N-acetyl-β-D-glucosaminidase activities. A depletion of renal glutathione content concomitant with a reduction in the activities of antioxidant and phase II metabolizing enzymes was detected. Lipid peroxidation, γ-glutamyl transpeptidase, adenosine deaminase and xanthine oxidase activities in renal tissue were markedly increased after Fe-NTA challenge. A significant deposition of iron in kidney and induction of serum prostaglandin E2 level were associated with the enhanced oxidative damage. Pretreatment of rats with either NS oil (2 mL/kg) or GT extract (100 mg/kg) by gavage for 7 consecutive days ameliorated most of the biochemical and histopathological changes induced by Fe-NTA. In conclusion, NS and GT can serve as potent chemopreventive agents to suppress oxidant-induced tissue injury and DNA damage.