The increasing role of copper oxide nanoparticles (CuO NPs) in many industries and their broad range of applications increase its potential toxic effects. Curcumin possesses a wide range of health benefits. This study aimed to evaluate the role of curcumin in attenuating CuO NPs toxicity in rat kidney. Thirty six animals were divided into five groups; control groups (I, II), curcumin group orally received curcumin 200 mg/kg bw, CuO NPs group orally gavaged 250 mg/kg bw CuO NPs and combined group orally gavaged curcumin and CuO NPs. Treatment was given for 3 months. Administration of CuO NPs revealed elevation in serum creatinine and blood urea nitrogen levels, elevated kidney and urine levels of kidney injury molecule‐1, decreased catalase, superoxide dismutase activities, total sulfhydryl, reduced glutathione content, increased serum reactive oxygen species, tissue total oxidant status, lipid hydroperoxides, protein carbonyl, malondialdehyde, nitric oxide levels, increased interleukin‐1β, tumor necrosis factor‐α, nuclear factor (NF‐κB), and decreased heme oxygenase‐1 (HO‐1) and γ‐glutamylcysteine synthetase (γ‐GCS) genes expression. Moreover, histopathological alteration in kidney structure was detected. Immunohistochemical‐stained sections by caspase‐3 reaction revealed apoptosis. Pretreatment with curcumin improved most of the adverse effects in rats treated with CuO NPs regarding oxidative stress and inflammatory indices in kidney, and kept histopathological‐ and immunohistochemical‐stained sections near to normal. This study shows that curcumin administration attenuates the toxicity in the kidney of CuO NPs‐treated rats through its antioxidant, anti‐inflammatory, and antiapoptotic effects.