Objective: To investigate the neuroprotective effects of Syzygium aromaticum (S. aromaticum) extract (500 mg/kg) on AlCl3(300 mg/kg)-induced mouse model of oxidative stress and neurotoxicity. Methods: An ethanolic extract of S. aromaticum seeds was prepared and the active compounds were identified using nuclear magnetic resonance spectroscopy. BALB/c mice were divided into five groups (negative control, AlCl3-treated, self-recovery, AlCl3+S. aromaticum, S. aromaticum only; n=10) and treated with AlCl3and S. aromaticum extract. Expression of oxidative markers [Superoxide dismutase 1 (SOD1) and peroxiredoxin 6 (Prdx6)] and amyloid precursor protein (APP) in the hippocampus and cortex was evaluated via PCR. Histopathological assessment was performed to investigate the extent of neurodegeneration. Results: It was observed that AlCl3exposure increased the expression of APP770 while simultaneously down regulated the expression of APP695. AlCl3also induced a significant decrease (P<0.05) and an increase (P<0.05) in the expression level of SOD1 and Prdx6, respectively. A substantial decrease substantial (P<0.05) in the density of Nissl substance was also observed in cortex of the mice treated with AlCl3. Interestingly, treatment with S. aromaticum extract normalized the alterations in the expression level of SOD1, Prdx6 and APP isoforms and improved the neuronal structural damage. Conclusions: The results showed that S. aromaticum is a promising antioxidant and a neuroprotective agent.