The study investigated the bioactive ingredients and the anti-duck hepatitis A virus 1 (DHAV-1) mechanisms of Sophorae tonkinensis Radix et Rhizoma (STR) by network pharmacology (NP) and molecular docking (MD). The main bioactive ingredients of the STR were obtained using TCMSP database. Cytoscape 3.8.2 software was used for topology analysis and construction of the STR-active molecule-target interaction network. The STRING database and Cytoscape plotted Protein-protein interaction (PPI) networks. The key targets of STR were analyzed and enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, the main bioactive ingredients of the STR were verified by MD. The STR-DHAV-1 target network included 13 ingredients and 34 target genes. The key target gene is IL-6. KEGG analysis revealed that the main pathways included AGE-RAGE signaling pathway in diabetic complications, pathways in cancer, and C-type lectin receptor signaling pathway. MD results further verified that the main bioactive components identified in the STR were quercetin, kaempferol and matrine, which had higher binding activities to target. Network pharmacology and molecular docking studies revealed that quercetin, kaempferol and matrine were the main bioactive ingredients of STR and might play a crucial role in potential molecular DHAV-1 therapeutic mechanisms.