The objective of this study was to investigate the effects of Polygonum multflorum (PM) Thunb. on the learning and memory ability in one and seven-month-old male senescence accelerated mice (SAMP8). The mice were fed with two different diets for 18 weeks; they were casein dietary group (control group) and casein diet supplemented with PM extracts. Active shuttle avoidance test was performed to determine the learning and memory ability of the mice while the spongy degeneration and the lipofuscin, malondialdehyde, and total thiol levels of the brain were measured to evaluate the extent of the brain degeneration and oxidative status. Results of active shuttle avoidance test showed the mice fed with the PM extracts had significantly better learning and memory ability than the control group. The spongy degeneration and the lipofuscin and malondialdehyde concentrations of the mice in the PM groups were significantly lower than the control in both age groups, whereas the total thiol levels were higher but not significantly different. It was concluded that the supplement of the PM extracts could improve the learning and memory ability and reduce the brain pathological changes in mice. This might be due to the antioxidant phytochemicals of the PM extracts.