Bisphenol A (BPA) is a hazardous endocrine disruptor released into the environment during the production of certain plastics used for covering of food and beverage cans. In this work, we examined the protective benefits of selenium (Se) against intestinal damage induced by BPA in male rats. Rats were distributed randomly into four groups. The first group received corn oil and served as the control. The second group was administered Se (1 mg/kg body weight; BW). The third group was given oral BPA (50 mg/kg BW). In the fourth group, Se (1 mg/kg BW) and BPA (50 mg/kg BW) were administered simultaneously. This experiment lasted for eight weeks. Specimens from the large intestine were subjected to biochemical analysis of antioxidants and oxidative stress biomarkers, histological observation under light and transmission electron microscopy and immunohistochemistry to autophagy and apoptosis markers. The BPA-exposed group showed significantly elevated oxidative stress markers associated with significant decline of antioxidants in intestinal tissues. BPA resulted in histological alterations such as severe mucosal necrosis with massive inflammatory cell infiltration. Ultra-structurally, the same group showed severe loss of the cell organelles, shrunken nuclei, and abundant autophagosomes. Immunohistochemistry results demonstrated a strong reactivity of caspase-3 and LC3 in the BPA group in contrast to the reaction to p62, which was markedly diminished. These effects were mitigated in the BPAþSe group. We concluded that BPA’s harmful effects on the large intestine are caused by apoptosis and autophagy. Se may protect intestinal cells from these effects and could be a useful and trustworthy approach for reducing BPA toxicity.