Wugen decoction, a classic traditional Chinese medical diet, is widely used to prevent influenza A virus infection in China. However, the principal effective ingredients and potential mechanism of Wugen decoction remain unclear. Therefore, a systemic analysis-based approach combined with molecular docking and network pharmacology is used to elucidate the molecular mechanism of Wugen decoction in prevention of influenza A. The efficient bioactive and potential targets of Wugen decoction are initially retrieved from public databases and relevant references. To further analyze the core targets, a protein-protein interaction network is investigated through cluster screening, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and Gene Ontology analysis. Then the binding behaviors between crucial bioactive ingredients and core targets are obtained via molecular docking. Quercetin, stigmasterol, beta-sitosterol, genistein, oxalic acid, and daidzein with higher degrees are collected and screened from the “Herb-Ingredients” network. Meanwhile, AKT1, IL1B, IL6, INS, TNF, and VEGFA are identified from cluster screening and topological investigation. The coincident targets are primarily concentrated to biological processes including hydrogen peroxide, cellular response to synapse, and molecular function to cysteine-type endopeptidase activity involved in tumor necrosis factor receptor binding. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis manifests that the signaling pathways related to influenza A prevention are closely associated with tumor necrosis factor receptor binding, RNA polymerase II sequence-specific DNA binding transcription factor binding, and protein phosphatase binding. Molecular docking results highlight that the effective ingredients can spontaneously bind with the core targets. In all, the present research comprehensively illustrates the potential mechanism of Wugen decoction against influenza A virus infection with the ‘multicomponent-multitarget-multipathway’ mode. This research also provides an effective approach to uncover the scientific basis of Wugen decoction within food and health care industries.