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Background: Uncontrolled diabetes mellitus (DM) is accompanied by progressive cognitive deterioration mediated by neurodegeneration due to chronic hyperglycemia and subsequent oxidative damage. Oxidative stress damage due to high blood glucose is associated with functional and structural changes in the hippocampus, responsible for cognitive properties, leading to cognitive impairment. Edaravone is a potent antioxidant with neuroprotective properties that has mainly been used to treat amyotrophic lateral sclerosis and has been tested in many models associated with cognition deficits. Our study aimed to assess edaravone's potential neuroprotective activity to reverse memory impairment in a streptozotocin (STZ)-induced diabetic rat model. Methods: DM was induced by a single 50 mg/kg STZ intraperitoneal injection. Rats received edaravone intraperitoneally at 6 mg/kg/day, six days/week, for four weeks. The radial arm water maze behavioral test evaluated both learning and memory. Oxidative stress was evaluated by molecularly measuring hippocampus enzyme activities and biomarker levels. Results: Impairment of short- and long-term memory was observed in rats with STZ-induced diabetes, accompanied by decreased hippocampal superoxide dismutase and glutathione peroxidase activities and reduced/oxidized glutathione ratio. Edaravone significantly attenuated memory impairment (p 0.05). Conclusion: Edaravone prevented STZ-induced memory impairment and attenuated oxidative stress likely by restoring hippocampus antioxidant mechanisms.