This research aimed to assess curcumin (CUR) effects on fenitrothion (FNT), a broad-spectrum organophosphate insecticide, −induced hepatorenal damage. Thirty adult male Wistar rats were allocated at random to five equal groups orally administered distilled water containing 1% carboxyl methylcellulose, corn oil (1 mL/rat), CUR (100 mg/kg b.wt.), FNT (5 mg/kg b.wt.), or CUR + FNT. CUR and FNT were dosed three times a week for two months. At the end of this trial, blood and tissue samples (liver and kidney) were subjected to molecular, biochemical, and histopathological assessments. The results revealed that CUR significantly diminished the FNT-induced up-regulation of hepatic CYP1A1 and CYP1A2 transcriptional levels. Moreover, CUR significantly suppressed the increment of the serum levels of hepatic alanine aminotransferase, gamma-glutamyl transferase, and kidney damage indicators (urea and creatinine) in FNT-intoxicated rats. Furthermore, in the hepatic and renal tissues, CUR remarkably restored the FNT-associated depletion of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione S transferase, catalase, and superoxide dismutase). In addition, CUR notably reduced the FNT-induced increment in malondialdehyde content in the hepatic and renal tissues. Besides, the pathological aberrations in liver and kidney tissues resulting from FNT exposure were significantly abolished in FNT + CUR treated rats. Overall, CUR could be an effective ameliorative agent against negative pesticide impacts like FNT