Nowadays, there is a continuous and progressive global public exposure to acrylamide (ACR) due its presence in fried and backed food. Thermal preparation of sugar-rich food mostly initiates chemical reactions that yield dangerous chemicals. Of these chemicals arise acrylamide and its metabolite glycidamide. Those having a high affinity for binding to nervous tissues. The acrylamide-induced neurotoxicity involves reduction in proliferation of neuronal progenitor cells associated with apoptotic cell death. Concerning acrylamide-induced toxicity, preventive medicine research focused on natural antioxidants. Studies on active constituents of Saffron showed obvious antioxidant, and anti-toxic properties. Here, we designed this study to investigate the possible protective effect of saffron against acrylamide-induced neurotoxicity in hippocampal area of brain. Adult male albino rats were assigned equally into 4 groups (n = 8); control; saffron group; acrylamide (ACR)-administered group and combined ACR and saffron- treated group. Our results recorded molecular changes as a significant decrease on genomic DNA fragmentation in saffron co-administered group as compared to ACR-exposed group. The changes on DNA mutagenicity were studied by analyzing the random amplification of polymorphism of DNA that showed an elevated genomic integrity on rat co –administered saffron with ACR in contrast to those exposed to ACR only