Background and purpose: TwHF has been used in traditional Chinese medicines for treating CVD. However, the underlying pharmacological mechanisms of the effects of TwHF against CVD remain to be elucidated. The aim of the present study is to reveal the pharmacological mechanisms of TwHF acting on CVD based on a pharmacology approach. Experimental approach: The active compounds were screened by TCMSP according to ADME. The potential targets of TwHF were predicted by SwissTargetPrediction database. The CVD-related therapeutic targets were obtained by the DrugBank, the OMIM database and the GeneCards database. PPI network was constructed by STRING database. GO and KEGG pathway enrichment analyses were performed by R package. The network of drug‐targets-diseases-pathways was constructed by Cytoscape software. Key results: A total of 51 effective ingredients of TwHF and the 178 common targets of TwHF and CVD-related were collected. AKT1, APP, MAPK, PIK3CA and TP53 was identified the core targets involved in the action of TwHF on CVD. Top ten GO and KEGG pathways were identified with a P value ≤ 0.01. Finally, we constructed the network of TwHF-targets-CVD-GO-KEGG. Conclusion and implications: Our results demonstrated that the main active compound of TwHF exerts cardiovascular protective effects and the core targets and pathways associated with the effects of TwHF on CVD. By the construction of the network of TwHF-targets-CVD-GO-KEGG, network pharmacology uncovered the pharmacological mechanisms of the action of TwHF on CVD and indicated a novel perspective to identify the intricate interactions among TwHF, candidate targets and related pathways.