Introduction: Bisphenol A (BPA), as an endocrine disruptor, found in packaging materials for food and drugs is of public health concern. It accounts for the majority of daily human exposure. Health problems associated with BPA exposure in humans includes reproductive issues, changes in hormone levels and various cancers. Recognized therapeutic effects of melatonin have been established but limited study has been conducted on their protective potentials on BPA toxicity therefore this study was carried out to investigate the effect of 5-methoxy-N-acetyl-tryptamine on bisphenol a induced epigenetic changes in wistar rats. Methods: Thirty five (35) adult albino rats was distributed into seven (7) groups of five (5) rats each: G1 (control), G2 (0.05 mg/kgbw/dy of BPA), G3 (10 mg/kgbw/dy daily of BPA) G4 (0.05 mg/kgbw/dy each of BPA and Melatonin), G5 (10 mg/kgbw/dy daily each of BPA and Melatonin), G6 (0.05 mg/kgbw/dy of Melatonin), G7(10 mg/kgbw/dy of Melatonin). Treatments were administered orally for 30 days. Haematological indices; haematocrit and hemoglobin were analysed. Histopathological examination of the testes, liver and brain were carried out. Epigenetic changes were measured using global DNA methylation kits. The results were analysed using descriptive statistics and ANOVA at ?0.05 . Results: Haematocrit (26.9 ± 4.7%) and haemoglobin (8.98 ± 1.57 g/dl) were significantly reduced in G3 when compared with the control group (54.2 ± 3.8% and 18.06 ± 1.28 g/dl), respectively. These effects were considerably mitigated in G4 (44.70 ± 6.20% and 13.56 ± 2.06 g/dl) and G5 (42.3 ± 4.4% and 14.10 ± 1.47 g/dl), respectively. GSH was significantly reduced in G3 but this effect was considerably corrected in G4 and G5. The G3 (5.16 ± 0.12 nM) showed higher methyl group, while lower distributions of methyl group were observed in G4 (4.16 ± 0.31 nM), G5 (4.01 ± 0.11 nM) and G7 (3.03 ± 0.11 nM), respectively. There was severe portal and sinusoidal congestion, with degeneration of hepatic cells in the liver, mild congestion of the testicular vessel and a hemorrhage of the meninges with congestion of the capillaries in the brain of G3, while these effects were completely mitigated in G5. Conclusion: The result of this study showed that melatonin demonstrated mitigative potentials on bisphenol a toxicity and prevented epigenetic changes in wistar rats.