Abstract: OBJECTIVE To explore the target and pathway of Epimedii Folium in the treatment of Alzheimer's disease(AD) based on network pharmacology, and to clarify its mechanism. METHODS The effective components and target genes of Epimedii Folium were screened by TCMSP database and Uniprot database. The target genes of AD were screened by Drugbank, Dis Ge NET and TTD databases. After mapping the component target with the disease target point, Cytoscape 3.7.1 software was used to construct the drug active component-target protein interaction network, at the same time, the STRING database was used to draw the target protein-target protein interaction network. The target protein was analyzed by GO and KEGG using Metascape database. Finally, the main results of network pharmacology were verified by MTT and real-time quantitative PCR. RESULTS Twenty-three effective components of Epimedii Folium were screened, 239 effective targets of Epimedii Folium and 2 156 therapeutic targets for AD were predicted. The 152 therapeutic targets of Epimedii Folium for AD were obtained after intersection. Protein interaction analysis indicated that GSK3β, AKT1, CDK5, CDK5R1, APP, MAPK1 and MTOR were the core targets of protein interaction network. The core targets of Epimedii Folium mainly involved AD, β-amyloid aggregation, abnormal phosphorylation of Tau protein, inflammatory response, oxidative stress, and apoptosis. Cell experiments suggested that Epimedii Folium could significantly increase the cell survival rate of PC12 cells induced by Aβ_25-35, and participate in the regulation of GSK-3β, AKT1, CDK5-mediated β-amyloid aggregation and Tau protein phosphorylation pathway. CONCLUSION Epimedii Folium has the characteristics of multi-active components, multi-targets and multi-pathways in the treatment of AD. This study provides a scientific basis for systematically elucidating the mechanism of Epimedii Folium in the treatment of AD.