Diabetes mellitus is a chronic disease involving persistent hyperglycemia, which causes an imbalance between reactive oxygen species and antioxidant enzymes and results in damage to various tissues, including the brain. Many societies have traditionally employed medicinal plants to control the hyperglycemia. Pouteria ramiflora, a species occurring in the savanna biome of the Cerrado (Brazil) has been studied because of its possible ability to inhibit carbohydrate digestion. Rats with streptozotocin-induced diabetes treated with an alcoholic extract of Pouteria ramiflora show an improved glycemic level, increased glutathione peroxidase activity, decreased superoxide dismutase activity, and reduced lipid peroxidation and antioxidant status. The extract also restored myosin-Va expression and the nuclear diameters of pyramidal neurons of the CA3 subregion and that of the polymorphic cells of the hilus. We conclude that Pouteria ramiflora extract exerts a neuroprotective effect against oxidative damage and myosin-Va expression and is able to prevent hippocampal neuronal loss in the CA3 and hilus subfields of diabetic rats. However, future studies are needed to understand the mechanism of action of Pouteria ramiflora extract in acute and chronic diabetes.