To observe the effect of puerarin on learning and memory function and tau phosphorylation in APP/PS1 transgenic mice, drugs were administered to 3-month old APP/PS1 transgenic mice. Learning and memory function of mice were assessed by Morris water maze test 3 months after treatment. Animals were decapitated after behavioral test. The levels of Aβ were detected by ELISA, the expression of protein [tau, phosphorylated tau, GSK3β and p-GSK3β(Ser9)] were assessed by Western blot. Morris water maze test showed that the escape latency of APP/PS1 double transgenic mice was significantly longer than that of the normal control group, and the residence time of the original quadrant was significantly shorter. The escape latency of puerarin group was significantly shorter and the residence time of the original quadrant was prolonged compared with the model group. Compared with the normal control group, the levels of Aβ in the cortex of APP/PS1 transgenic mice were increased, the expression of phosphorylated tau was significantly increased, and the expression of phosphorylated GSK3β(Ser9) protein was decreased. Treatment with puerarin, the latency of APP/PS1 transgenic mice was significantly reduced, the level of Aβ was decreased, the expression of phosphorylated tau was significantly decreased, and the expression of phosphorylated GSK3β(Ser9) protein was increased. Puerarin improves the learning and memory impairment by reducing the formation of Aβ, activating the GSK3β signaling pathway, inhibiting the phosphorylation of tau in APP/PS1 double transgenic mice.