Aim: The combination of chemotherapeutics and pomegranate peel extract has been shown to have a stronger anti-cancer effect. However, there is no information about how pomegranate peel extract will affect the neurotoxicity that may develop due to cancer chemotherapy. In this study, we aimed to the effects of strong antioxidant pomegranate peel extract on paclitaxel induced primary neuron damage in newborn rats by biochemical and molecular analysis. Material and Method: Paclitaxel toxicity was induced in the primary neuron cell culture derived from newborn rats. PPE 200, 300 and 400 mg/ml doses were applied 2 hours before the paclitaxel for protective effect. Results: In the MTT analysis, paclitaxel reduced cell viability by caused neuronal damage at the end of 24 hours. PPE has demonstrated significant protective effect on cell viability by preventing paclitaxel toxicity at all doses. PPE was demonstrated its effects by reducing oxidative stress, increasing antioxidant capacity, and also by suppressing the TNF-α expression which is pro-inflammatory cytokine, and caspase 9 and 3 expression which are apoptotic proteins. Conclusion: PPE prevents primary neuron damage caused paclitaxel by its antioxidant, anti-inflammatory and anti-apoptotic effect.