ABSTRACT Methoxychlor (MXC) is a widely used organochlorine pesticide primarily targeting pests. However, MXC has been found to negatively impact the reproductive system of both humans and animals, triggering oxidative stress and apoptosis. Melatonin (MLT), an endogenous hormone, possesses various benefits, including circadian rhythm regulation and anti-inflammatory and antioxidative stress effects. Moreover, MLT plays a crucial role in the development of animal germ cells and embryos. This study aimed to investigate the impact of MLT on porcine oocytes exposed to MXC. The experimental findings revealed that 200 μM MXC had detrimental effects on the maturation of porcine oocytes. However, the addition of 10−8 M MLT mitigated the toxic effects of MXC. MXC induced oxidative stress in porcine oocytes, leading to an increase in reactive oxygen species and impairing mitochondrial function. Consequently, oocyte quality was affected, resulting in elevated levels of early apoptosis and DNA damage, ultimately negatively impacting subsequent embryonic development. However, the addition of MLT showed the potential to ameliorate the damage caused by MXC. In conclusion, our results suggest that MLT exhibits a protective effect against MXC-induced damage to porcine oocyte maturation.