AbstractFipronil is a phenylpyrazole insecticide that is widely used in agricultural, veterinary, and public health fields for controlling a wide variety of insect species and it is an environmentally potent toxic substance. Curcumin and quercetin, which are well-known natural antioxidants, are widely used to prevent the harmful effects of free radicals on biological systems. The present study aimed to determine the potential ameliorative effects of quercetin and/or curcumin on fipronil-induced nephrotoxicity in rats. Curcumin (100 mg/kg of body weight), quercetin (50 mg/kg of body weight), and fipronil (3.88 mg/kg of body weight) were administered to male rats by intragastric gavage for 28 consecutive days. In the present study, body weight, kidney weight, the renal function markers (blood urea nitrogen, creatinine, and uric acid levels) in the blood, antioxidant enzyme activities, and malondialdehyde level as markers of oxidative stress, and histological changes of the renal tissue were evaluated. The levels of serum blood urea nitrogen, creatinine, and uric acid were significantly increased in fipronil-treated animals. Additionally, while superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase activities were decreased in the kidney tissue of rats treated with fipronil, malondialdehyde level was significantly increased. Histopathological analyses showed that the glomerular and tubular injury occurred in the renal tissue of fipronil-treated animals. Also, the supplementation of quercetin and/or curcumin with fipronil significantly improved fipronil-induced alterations in renal function markers, antioxidant enzyme activities, malondialdehyde levels, and histological features of renal tissue.