Polygalasaponins are the major active constituents of Polygala tenuifolia exhibiting antiamnesic activity, but their applications are limited due to their toxicities. Evidence showed that the toxicities can be attenuated by hydrolysis. Herein, effects of a hydrolysate of polygalasaponins (HPS) on cognitive impairment induced by Aβ(25-35) were assessed by Morris water maze and step-through passive avoidance tests. The impaired spatial reference memory was improved by HPS (50 and 100 mg/kg). In the acquisition trial of step-through test, HPS (50 and 100 mg/kg) increased the latency into the dark chamber and decreased the error frequency significantly (P < .05). However, no significant change was observed during the retention trial. Additionally, HPS increased the corresponding SOD activities (62.34%, 22.09%) and decreased MDA levels (28.21%, 32.35%) in both cortex and hippocampus as compared to model animals. These results show that HPS may be a useful treatment against amnesia probably via its antioxidant properties.