One of the important organ damage of hypertension is cognitive decline. Cognitive function is determined by the function of hippocampus, and previous studies have suggested that the decrease in brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. Protection against cognitive decline is reported not only in pharmacological therapy but also in exercise training or calorie restriction. The aim of the present study was to determine whether exercise training plus calorie restriction cause synergistic protection against cognitive decline via BDNF in the hippocampus or not. Exercise training for 28 days improved cognitive decline determined by Morris water maze test via up-regulation of BDNF in the hippocampus of stroke-prone spontaneously hypertensive rats, whereas calorie restriction for 28 days did not. However, exercise training plus calorie restriction causes the protection against cognitive decline to a greater extent than exercise training alone. In conclusion, exercise training plus calorie restriction causes synergistic protection against cognitive decline via up-regulation of BDNF in the hippocampus of stroke-prone hypertensive rats.