Objective To investigate the interventional effect of betulin on the learning and memory functions and the expression of hippocampal synaptic function-related proteins in Alzheimer's disease (AD) mice, and to provide new insights into the treatment of AD.Methods APP/PS1 double transgenic mice were randomly divided into model group, high-dose betulin group, and low-dose betulin group. Healthy C57BL/6J mice were used as controls. The learning and memory abilities of the mice were determined by behavioral observation, and the bioelectricity of hippocampal neurons was measured by electrophysiological recording. In addition, neuronal apoptosis was measured by TUNEL staining, and postsynaptic density-95 (PSD-95) and synapsin-I expression was measured by real-time PCR.Results The water maze test showed that betulin improved the cognitive impairment of model mice. The amplitude of long-time potentiation (LTP) was lower in the AD model group than in the control group, but was higher in the betulin groups than in the AD model group. Compared with the control mice, the neuronal apoptosis rate was increased in the model mice but was reduced in the model mice treated with betulin. Furthermore, hippocampal expression of PSD-95 and synapsin-I was decreased in AD mice but was increased following betulin intervention.Conclusions Betulin can protect the cognitive function of APP/PS1 double transgenic mice with Alzheimer's disease by increasing the expression of PSD-95 and synapsin-I and enhancing the LTP of the hippocampus.