To evaluate the improvement effect of piceatannol on cognitive impairment in Alzheimer's disease (AD) mice, seventy-two male Kunming mice were randomly divided into 6 groups with 12 mice in each group, including control group, model control group, positive control group, piceatannol intervention groups (low-dose, medium-dose and high-dose). AD mice were induced by AlCl₃ and D-galactose intervention for 70 d. After 5 weeks of continuous intervention with piceatannol on the 35th day of modeling, Morris water maze experiment was used to test the spatial learning and memory ability of mice. Meanwhile, the protein expression levels of Aβ1-42 and TNF-α in the hippocampus of mice were determined by ELISA method, and the activity of superoxide dismutase (SOD) and content of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in mice serum were detected. Combined with relative viscera index, the improvement effect of piceatannol on AD mice was analyzed. The results showed that the latency of escape in model control group was significantly higher than that in control group and the memory ability was significantly decreased, while piceatannol effectively improved the cognitive behavior and memory ability of AD model mice (P<0.01). Compared with control group, the levels of Aβ1-42, TNF-α and activated microglia were significantly increased in model control group, while piceatannol significantly decreased the levels of Aβ1-42, TNF-α and activated microglia (P<0.01). Moreover, piceatannol effectively increased the activities of SOD and the content of GSH-Px and reduced MDA content in mice serum, and alleviated oxidative injury. In conclusion, piceatannol can improve the cognitive function of AD mice by reducing oxidative stress, neuroinflammation and Aβ production in the hippocampus.