To examine the effect of consuming polyphenol-rich Oriental plum (Prunus salicina Lindl) on the cognitive performance and the expressions of cerebral neurodegeneration-related proteins in diabetic rats, Wistar rats were assigned into 4 groups: control (C, n = 14), nicotinamide/streptozotocin-induced DM rats (DM, n = 13), DM rats fed metformin (0.05% w/w in the diet, MT, n = 18), and DM rats fed freeze-dried oriental plum powder (2% w/w in the diet, OP, n = 16) for 2 months. The cognitive performance was evaluated by testing in a Morris water maze. The insulin resistance, serum lipid peroxidation, expressions of pathological proteins of AD, beta-amyloid (Aβ) and phosphorylated tau protein were also measured. Consumption of plums significantly improved the spatial learning ability, reduced the insulin resistance, lipid peroxidation, Aβ and phosphorylated tau protein expressions in the cerebral cortex (all P < 0.05), and decreased Aβ deposition in the hippocampus of diabetic rats. In conclusion, polyphenol-rich Oriental plums ameliorated the cognitive decline and reduced the expressions of pathological proteins of AD by possibly reducing hyperglycemia, insulin resistance, and oxidative stress in diabetic rats.