This study was conducted to evaluate the effects of exposure to diphenyl diselenide (PhSe)2 on cognitive impairment induced by scopolamine, a muscarinic antagonist, using the Y-maze and Morris water maze tests in mice. One hour before the tests, mice were treated with (PhSe)2 (50 mg/kg, oral) and 30 min later memory impairment was induced by administration of scopolamine (1 mg/kg, intraperitoneal). (PhSe)2 (50 mg/kg, oral) significantly improved scopolamine-induced memory impairment in the Y-maze test. At the probe trial session in Morris water maze, (PhSe)2 (50 mg/kg, oral) significantly decreased the escape latency, increased the number of crossings in the platform local, and increased the time spent in the platform quadrant when compared with the scopolamine-treated group. General locomotor activity was similar in all groups. This study showed that (PhSe)2 ameliorated the impairments of spatial long-term memory and short-term memory, showed by the performance of mice in the Morris water maze and Y-maze tasks, respectively. These results suggest that (PhSe)2 may be useful for the treatment of cognitive impairment that may hold significant therapeutic value in alleviating certain memory deficits observed in Alzheimer's disease.