The use of coloring agents in food industry has dramatically increased. Children are the main consumers of colored food products and beverages and are more vulnerable to the effects of synthetic colorants. Curcumin, an active constituent of turmeric plant, has been the subject of extensive studies assessing its antioxidant properties. The present study was conducted to evaluate the protective potentials of curcumin against neurotoxicity induced by the synthetic food colorant; tartrazine. Thirty-six young male albino rats were divided into six groups; negative control (Group I), distilled water (Group II), corn oil (Group III), curcumin (Group IV), tartrazine (Group V) and tartrazine+curcumin (Group VI). At the end of the study, the rats were subjected to biochemical, histological and immunohistochemical staining for GFAP. Our results showed that tartrazine induced a significant decrease in GSH, serotonin and GABA levels and a significant increase in MDA levels in the brain as compared to control groups. Tartrazine induced apoptosis, vacuolations, congestion and cellular infiltration in the brain tissue. An immunohistochemistry study showed astrogliosis with increased expression of GFAP. Curcumin ameliorated all these effects. In conclusion, tartrazine is neurotoxic. Increased brain oxidative stress and cellular damage are contributing factors. Curcumin can prevent tartrazine-induced neurotoxicity.