Acrylamide (ACR) became an environmental pollutant due to huge and progressive exposure for both experimental animals and humans. Alternative medicine research paid more attention to natural antioxidants. Saffron exhibited obvious antioxidant and medically-beneficial properties. Here, the present study aimed to investigate the possible neuro-protective effect of saffron against acrylamide-induced histopathological alterations in hippocampal tissue of albino rats. Adult male albino rats were categorized equally into 4 groups (n = 8); control, saffron, ACR and ACR + saffron groups. Our results recorded histopathological changes due to exposure of rats to ACR toxicity in hippocampus. The pyramidal cells of Ammon’s horn (CA1- CA4) appeared degenerated and necrotic with hemorrhage, decreased thickness and increased vacuolization concomitant to shrinkage and damage of these neurons. The dentate gyrus, in its turn, appeared more affected by ACR exposure of experimental animals at the cellular level where darkly-stained and degenerated granular cells with vacuolization could be detected. Conclusion; the present study confirmed ACR-induced neurotoxicity in rats (50 mg/kg) and suggested the use of saffron extract (80 mg/kg) to prevent or delay neurological damages induced by ACR exposure.