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.