Background: Many physiological properties of pomegranate peel which has a strong antioxidant effect have been shown. We aimed to investigate the effects of pomegranate peel, a potent antioxidant on the neurotoxic effect of glutamate, an excitatory neurotransmitter. Methods: In our study, the newly born rat brain cortex was used. Pomegranate peel extract were used 200, 300 and 400 mg / ml dose after 2 hours 6x10-3 and 3x10-3M concentration glutamate application was performed. After 24 hours of toxicity, viability test, total oxidant and antioxidant capacity measurements were performed. Results: Glutamate application significantly reduced cell viability in increased doses, while pomegranate peel extract revealed the best neuroprotective effect in high doses. Increased total oxidant capacity due to toxicity has been significantly improved with pomegranate peel application. Decreased antioxidant capacity due to glutamate has improved with pomegranate peel extract. Pomegranate peel extract alone had a proliferative effect when high doses were applied. The pomegranate peel has demonstrated its neuroprotective effects by suppressing the proinflammatory cytokine tumor necrosis factor-α and the expression of apoptotic proteins, caspase 9 and 3. Conclusion: Pomegranate peel extract inhibited glutamate-induced neurotoxicity due to its antioxidant, anti-inflammatory and anti-apoptotic effect.