Aluminum is the most abundant metal on earth, known for its toxicity to humans and laboratory animals. Melatonin, produced by the pineal gland, has been shown to be an effective antioxidant. In this study, we investigated the possible protective role of melatonin in modulating toxicity and oxidative stress induced by chronic exposure to aluminum in the small intestine of rats. Wistar albino rats were divided into five groups. Group I served as the control and received only physiological saline, Group II served as the control for the melatonin group and received ethanol and physiological saline, Group III received melatonin, Group IV received aluminum sulfate, and Group V received aluminum sulfate and melatonin, injected three times per week for 1 month. Administration of aluminum caused degenerative changes in small intestine tissues, such as histological damage, increase in metallothionein immunoreactivity, and decrease in cellular proliferation index. Moreover, intestinal glutathione levels, and catalase, superoxide dismutase, glutathione peroxidase, sodium/potassium-ATPase, and glucose-6-phosphate dehydrogenase activities decreased, while lipid peroxidation and myeloperoxidase levels, and alkaline phosphatase, lactate dehydrogenase, and xanthine oxidase activities increased in the aluminum group. Administration of melatonin mostly prevented these effects. Consequently, we can say that melatonin protects the intestine from aluminum toxicity through its antioxidant and proliferative effects.