This study aims to explore the mechanism of the Andrographis Herba (AH) in the treatment of inflammatory bowel disease (IBD) based on network pharmacology and experimental verification. The potential targets of AH in the treatment of IBD were screened through databases such as TCMSP. The core targets were analyzed through GO biological function annotation and KEGG pathway enrichment. The protein-protein interaction network was constructed using STRING database. The Molecular docking technology was used to simulate the binding ability of AH active compounds and key target proteins. Furthermore, Western blot and ELISA methods were used to verify the key therapeutic effect of AH on IBD. After screening and analysis, 22 AH active compounds such as wogonin (WOG) were obtained. The key targets for the treatment of IBD included phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), mitogen-activated protein kinase 3 (MAPK3), and Serine/threonine kinase 1 (AKT1). The GO enrichment indicated that the potential targets of AH in the treatment of IBD were mainly involved in the biological processes of protein phosphorylation, which occurred at the plasma membrane, and exerted molecular functions mainly through ATP binding. KEGG pathways enrichment suggested that it is mainly closely related to the phosphoinositide 3-kinase (PI3K)-AKT signaling pathway. AutoDock was used to perform molecular docking between the best active compound WOG and the key targets, and the results showed that the binding energy of MAPK1 (-5.09 kcal/mol) and AKT1 (-4.94 kcal/mol) was the best. In vitro experiments showed that AH and WOG decreased the expression of inflammatory factors by inhibiting the AKT/extracellular regulated protein kinases 1/2 (ERK1/2) signaling pathway. This study comprehensively reveals the potential active compound WOG of AH in the treatment of IBD for the first time, and explores its potential molecular mechanism, which provides the theoretical basis and research direction for further exploration of its mechanism of action.