This study explored the mechanism of action of Sargent gloryvine extract in treating severe pancreatitis. We used the PubChem and SwissTargetPredicton databases to predict the potential targets. The database for Annotation, Visualization, and Integrated Discovery was used to perform Gene Ontology. The Kyoto Encyclopedia of Genes was used to perform Genomes enrichment analyses. These analyses, visualized via Cytoscape software followed by molecular docking validation, identified Salidroside, Lignans, Emodin, and Physcion as key active compounds in the extract. The protein-protein interaction network analysis highlighted tumor necrosis factor, interleukin-6, and nuclear factor κB as critical targets with 42 signaling pathways identified as relevant. The nuclear factor κB pathway emerged as especially significant in the extract's effect on severe pancreatitis. Enrichment analysis screened 42 related signaling pathways, among which the nuclear factor κB pathway may play a vital role in treating severe pancreatitis with Sargent gloryvine extract. The molecular docking results indicated an excellent binding activity between Sargent gloryvine extract and nuclear factor κB. In conclusion, the therapeutic approach of Sargent gloryvine extract in severe pancreatitis involves a complex interaction of multiple components, targets, and pathways, with a potential mechanism linked to the downregulation of the nuclear factor κB signaling pathway.