Background: Food coloring agents used in food remain controversial because many adverse effects are encountered. Therefore, the objective of the present study was to investigate whether curcumin has potential protection against oxidative stress, organ damage, and genotoxic effects induced by different doses of tartrazine, a synthetic food coloring agent, in male rats. Experimental procedure: Six groups were established as follows: Group 1 represented the control. Groups 2 and 3 were given tartrazine orally, with a daily dosage of 10 and 20 mg/kg b.w., respectively. Group 4 was given orally a daily dose of 50 mg curcumin/kg b.wt. Groups 5 and 6 were orally given daily doses of 10 and 20 mg/kg tartrazine and co-treated with 50 mg/kg curcumin, respectively. Results: The administration of low and high dose tartrazine for 30 and 60 days significantly increased the following parameters in proportion to the dose and time of exposure: body weight; levels of AST, ALT, urea, creatinine, reactive oxygen species, and lipid peroxidation; and reduced organ weight (liver, kidneys, and testes), concentrations of total protein, albumin, catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), free and total testosterone, sperm count, motility, and viability. Furthermore, tartrazine induced histopathological alterations and DNA damage in hepatic, renal and testicular tissues. Co-treatment of rats with curcumin and tartrazine revealed milder pathological alterations compared to rats treated with tartrazine alone. Conclusion: Taken together, this study showed that curcumin ameliorated the tartrazine-induced toxicity in the liver, kidney, and testis of male rats