is a classic cumulative nephrotoxicant and literature suggests that its toxicity is associated with oxidative stress and inflammation which contribute to pathologies in various tissues. We sought to investigate whether polyphenols isolated from virgin coconut oil (VCO) would modulate nephrotoxicity and inflammation induced by Cd in rats. Methods: Rats were administered polyphenols prior to and along with Cd (5 mg/kg, orally) for 7 weeks. Serum markers of renal damage, interleukin-6 (IL-6), C-reactive protein (CRP) and nitric oxide (NO) were evaluated; renal activities of antioxidant enzymes, as well as malondialdehyde (MDA) and reduced glutathione (GSH) content were determined. Histopathologic alterations were evaluated to define kidney damage. Results: Cadmium exposure induced nephrotoxicity and oxidative stress evident by significantly increased serum levels of creatinine, urea, and uric acid along with remarkable depression in renal activities of antioxidant enzymes and GSH with prominent increase in MDA. Inflammatory markers -IL-6, CRP and NO were significantly increased and confirmed by histopathology. Sub-chronic administration of VCO polyphenols attenuated the Cd-induced biochemical alterations compared to Cd control with remarkably improved histopathological observations. Conclusion: The findings showed that VCO polyphenol supplementation protects against Cd-induced nephrotoxicity via its antioxidant and anti-inflammatory mechanisms in rats.