Background Using network pharmacology，systematicly reveals the Mechanisms of Radix Isatidis in the therapy of coronavirus disease 2019 （COVID-2019）. Methods The active components and targets of Radix Isatidis were obtained by searching the Batman, TCMSP, and SwissTargetPrediction databases, and COVID-19 related targets were searched through Genecards, Drugbank, and Malacards database. After that, we used String database to establish protein-protein interaction, using David database to conduct enrichment analysis of gene ontology and pathway enrichment analysis based on the Kyoto encyclopedia of genes and genomes. The molecular docking was performed using ChemOffice, PyMOL, and Auto Dock software. Result A total of 73 active ingredients and 1584 related gene targets of Radix Isatidis were screened from kinds of databases while 559 gene targets of COVID-19 were picked out. Among them, there are 70 of the same targets. According to the GO enrichment analysis(P≤0.01), 35 of them belong to biological process, 13 of them belong to cell component, and 14 of them belong to molecular function. And for KEGG analysis, 22 pathways were obtained(P≤0.01), including PI3K − Akt signaling pathway andHIF − 1 signaling pathway. Conclusions Radix Isatidis may act on the PI3K − Akt signaling pathway and HIF−1 signaling pathway Through direct or indirect regulation of the above goals and ways to play role in the therapy of COVID-19