Shufeng Jiedu capsule (SFJDC) is a well-known Chinese patent drug that is recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. However, the exact molecular mechanism of SFJDC remains unclear. The present study aims to determine the potential pharmacological mechanisms of SFJDC in the treatment of COVID-19 based on network pharmacology. The network pharmacology-based strategy includes collection and analysis of active compounds and target genes, network construction, identification of key compounds and hub target genes, KEGG and GO enrichment, recognition and analysis of main modules, as well as molecule docking. A total of 214 active chemical compounds and 339 target genes of SFJDC were collected. Of note, 5 key compounds ( β -sitosterol, luteolin, kaempferol, quercetin, and stigmasterol) and 10 hub target genes (TP53, AKT1, NCOA1, EGFR, PRKCA, ANXA1, CTNNB1, NCOA2, RELA and FOS) were identified based on network analysis. The hub target genes mainly enriched in pathways including MAPK signaling pathway, PI3K-Akt signaling pathway and cAMP signaling pathway, which could be the underlying pharmacological mechanisms of SFJDC for treating COVID-19. Moreover, the key compounds had high binding activity with three typical target genes. By network pharmacology analysis, SFJDC was found to effectively improve immune function and reduce inflammatory responses based on its key compounds, hub target genes, and the relevant pathways. These findings may provide valuable evidence for explaining how SFJDC exerting the therapeutic effects on COVID-19, providing a holistic view for further clinical application. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.