Objective To investigate the active ingredients, core targets, and potential mechanisms of mudan cortex in treatment of corona virus disease 2019(COVID-19) based on network pharmacology and molecular docking. Methods The Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to obtain the main active ingredient compounds and targets of mudan cortex, and the GeneCards® and OMIM® databases were used to obtain COVID-19-related targets, and the potential targets of mudan cortex for COVID-19 treatment were obtained by intersecting the above two. The potential targets were input into the STRING database to obtain the interactions of the target proteins in the biological sys‐ tem and to build a PPI network, and the COVID-19-mudan cortex-active ingredient-target network was diagrammed using Cytoscape software. GO and KEGG enrichment analyses were performed on the potential targets to obtain the relevant gene functions and signaling pathways. The Discovery Studio 2019 software was used to perform molecule-protein docking of the main active components of mudan cortex in the target network diagram and the clinically used drugs Nematovir and Raltegravir in treatment of COVID-19 with the important targets of COVID-19 3CL protease and angiotensin-converting enzyme 2(ACE2). Results A total of 6 active ingredients of mudan cortex, quercetin, mairin, sitosterol, kaempferol,(+)-cat‐ echin, and 5-[[5-(4-methoxyphenyl)-2-furyl]methylene]barbituric acid and 150 their related targets were obtained, and 716 targets related to COVID-19 were intersected to obtain 36 potential targets of mudan cortex for the treatment of COVID19. The PPI diagram showed that the core proteins were mainly VEGFA, IL-6, and IL-1B. The COVID-19-mudan cortexactive ingredient-target network diagram showed that the active ingredients of mudan cortex for COVID-19 were sequential‐ ly, quercetin, kaempferol, barbituric acid, and (+)-catechin, with the main targets of PPARG, PTGS2, and estrogen re‐ ceptor 1(ESR1). GO and KEGG enrichment analysis obtained 61 molecular functions and 109 signaling pathways. The molecular functions mainly included cytokine receptor binding, DNA-binding transcription factor binding, and signaling receptor activator activity. The signaling pathways mainly included lipids and atherosclerosis, IL-17, and tumor necrosis factor (TNF) family, etc. The molecular-protein docking results showed that the barbituric acid and quercetin had a more stable binding capacity to 3CL protease and ACE2, respectively, in comparison with Nematovir and Raltegravir. Conclu⁃ sion Mudan cortex exerts a therapeutic effect on COVID-19 through the active ingredients quercetin, barbituric acid, (+)-catechin, and kaempferol acting on PPARG, PTGS2, and ESR1, etc., and the mechanisms are mainly related to lip‐ ids and atherosclerosis, IL-17, TNF, and other pathways. [ABSTRACT FROM AUTHOR]