Objective To explore the mechanism of andrographis paniculata treatment for coronavirus disease 2019 (COVID-19) based on network pharmacology. Methods The TCMSP database was used to screen active pharmaceutical ingredients and targets of andropona paniculata. The GeneCards database was applied to search the target of COVID-19. The Uniprot database was applied to standardize the target protein genes. Intersection targets of drug targets and disease targets were taken to obtain potential therapeutic targets, therapeutic targets were imported into String database to construct protein interaction network diagram, and Cytoscape-V3.8.0 software was used for visual analysis. Metascape and DAVID databases were used for GO and KEGG enrichment analysis of treatment targets. Results It was found that there were 24 main active components of Andrographis paniculus, 66 drug targets corresponding to the active components, 259 disease targets for COVID-19, and 18 potential therapeutic targets were obtained from the intersection. Through the construction of protein interaction network diagram, it was concluded that the the most interaction genes were TNF, MAPK14, CASP3, IL6, and PPARG. Two of the most important genes, PPARG and NOS2, are most closely related to the target and the drug. A total of 157 biological processes, 25 molecular functions and 15 cell components were obtained through GO enrichment analysis, mainly including cell response to LPS, glucocorticoid response, inflammatory response, DNA damage, etc. KEGG enriched 86 pathways, such as endogenous and exogenous apoptosis signaling pathway, NOD receptor signaling pathway, influenza A signaling pathway, etc. Conclusion This study suggests that andrographis paniculorum can treat COVID-19 through multiple targets and pathways, and its mechanism may be related on anti-inflammatory, immunological and anti-apoptotic.