Background and Objective: Methylenedioxymethamphetamine (MDMA) is used by millions of people worldwide as a recreational drug. Due to the popularity of MDMA use and its potential to create long-lasting or permanent 5-HT axon damage, the need for ways to control its effect on the brain is crucial. The present study aimed at investigating the effect of Moringa oleifera aqueous leaf extract on MDMA-induced neurotoxicity in the prefrontal cortex. Materials and Methods: Thirty adult male Wistar rats were randomly divided into 5 groups, A, B, C, D and E (n = 6) which were treated every day for 2 weeks. Group A: Control group, Group B: Moringa only (200 mg kgG1 ), Group C: MDMA only (5 mg kgG1 ), Group D: MDMA for the first 1-7 days (5 mg kgG1 ), moringa for the remaining 8-14 days (200 mg kgG1 ) and Group E: MDMA in the morning (5 mg kgG1 b.wt.) and moringa in the evening (200 mg kgG1 ). Brain samples were collected and weighed and the prefrontal cortex was sliced, sectioned and processed for histological and immunochemical analysis. Results: The MDMA caused neuronal and myelin sheath degeneration. Moringa, however, promoted the regeneration of myelin sheaths and neurons to reverse damage caused by MDMA. Conclusion: The result showed that M. oleifera aqueous leaf extract protected and also ameliorated neurotoxicity caused by MDMA.