Nickel (Ni) is an important environmental toxicant that can cause cancer and cardiovascular disease. The aim of this study was to examine the protective effects of troxerutin (Txn) Ni-induced renal dysfunction in rats using biochemical and histopathological approaches. Nickel (20 mg/kg body weight [b.w.]/day) was administered intraperitoneally (i.p.) for 20 days. Renal damage from Ni toxicity was evident from the changed levels of serum and urinary markers in Ni-treated rats. The levels of lipid peroxidation markers also significantly increased, while the levels of nonenzymatic and enzymatic antioxidants significantly decreased in the kidney of Ni-intoxicated rats. Troxerutin was administered orally (100 mg/kg b.w.) for 20 days along with Ni, resulting in a reversal of Ni-induced biochemical changes in kidney accompanied by a significant decrease in lipid peroxidation and an increase in the level of renal antioxidant defense system. Histopathological studies in the kidneys of rats also showed that troxerutin (100 mg/ kg b.w.) markedly reduced the toxicity of Ni and preserved the normal histological architecture of the renal tissue. The present study results suggest the nephroprotective potential of Txn in Ni toxicity, which might be due to its antioxidant and metal-chelating properties.