〔Abstract〕 Objective To investigate the effects of cynomorium songaricum extract on cognitive dysfunction of Alzheimer disease(AD) model mice based on network pharmacology and animal experiments. Methods Network pharmacology was used to predict the related targets and signal pathways of the extract of cynomorium songaricum to improve AD. Senescence accelerated mice P8(SAMP8) were selected as the model of AD. Based on the results of the preliminary experiment, 0.17 g/(kg·d) was selected as the optimal dosage for the extract of cynomorium songaricum. The extract of cynomorium songaricum [0.17 g/(kg·d), Donepezil hydrochloride [2.0 mg/(kg·d)] and normal saline were given orally for 28 days according to the groups. Morris water maze evaluated the learning and cognitive function of animals. The number of neurons in cornu ammonis 1(CA1) of hippocampus was observed by Nissl staining. The expression of recombinant Beclin 1(Beclin-1), Sequestosome 1(p62), light chain 3(LC-3) protein was detected by immunohistochemical method. The protein expression levels of phosphoinositide 3-kinase(PI3K), protein kinase B(AKT) and glycogen synthase kinase3β(GSK-3β) in the hippocampus of mice in each group were detected by Western blot. Results Based on the network pharmacology study, it was predicted that the biological mechanism of cynomorium songaricum to improve AD might be the regulation of autophagy, and the possible signaling pathway was PI3K/AKT/GSK-3β. The results of animal experiments showed that the extract of cynomorium songaricum could improve the spatial memory learning ability of AD model mice, improve the damage of hippocampal neurons, significantly increase the number of neurons, and increase the expression levels of PI3K, p-AKT/AKT, p-GSK-3β/GSK-3β, Beclin-1 and LC3 in the hippocampus of mice. The expression level of p62 decreased. There was no significant difference between male and female mice during the experiment. Conclusion The extract may improve the cognitive dysfunction of male and female AD models by activating autophagy mediated by PI3K-AKT-GSK-3β signaling pathway, and there is no significant gender difference in the effect.