Reproduction is considered the means through which genetic material is transferred from one generation to another, and since the reproductive rate determines the success or failure of breeding systems, attention must be directed toward the reproductive system of males and females and improving productive and reproductive efficiency, thus it represents a biological and economic challenge. The aim of this article is to clarify the complex relationship between three main factors: nutrition (which leads to negative energy balance), stress (which leads to oxidative stress), and the hormone melatonin and its role as a molecular protective mediator. Research has reported that after calving, negative energy balance negatively affects reproductive hormones. Recently, the resumption of reproduction is associated with metabolic and heat stress that increase the production of reactive oxygen species (ROS), thus causing oxidative stress that leads to oocyte damage. Here we highlight melatonin hormone, due to its antioxidant properties, as a defensive mechanism to reduce oxidative effects and improve oocyte and ovarian function. Understanding the mechanism of these three factors is important for improving modern nutritional and management strategies to enhance reproduction and productivity in the herd.