Network pharmacology and molecular docking methods were used in the present study to clarify the molecular mechanism of two traditional Chinese medicine prescriptions of climacteric syndrome. Based on oral availability and drug similarity, the main active components of Erzhi Pill and Erxian Decoction were screened through the platform of traditional Chinese medicine system pharmacology. The target database of climacteric syndrome was established by using GENECARD, OMIM, PharmGKB, Targets and Drugbank. The “component – target” network diagram was constructed using Cytoscape software (version 3.8.2). Topology analysis, module analysis, and GO and KEGG enrichment analyses were used to explore the core target and action pathway of Erzhi Pill-Erxian Decoction for treating climacteric syndrome of same disease with different treatments. There were 16 active components and 103 corresponding targets found in Erzhi Pill; 69 active components and 121 corresponding targets were found in Erxian Decoction; and 100 potential targets were found in Erzhi Pill and Erxian Decoction. Through network analysis, topology and module analysis, TP53, AKT1, Jun, ESR1, IL1B, CASP3, MMP9, PTGS2, HIF1A, MYC and EGFR could be considered as potential targets of the 2 prescriptions for alleviating climacteric syndrome. The effects of Erzhi pill and Erxian Decoction on climacteric syndrome are mainly in the pathway of lipid and atherosclerosis, AGE-RAGE signaling pathway and PI3K-Akt signaling pathway in diabetic complications. The active components in Erzhi Pill - Erxian Decoction, such as quercetin, show considerable potential as a candidate drug for the treatment of climacteric syndrome.