Background: Lianhua Qingwen Capsules (LHQW) is a traditional Chinese medicine prescription commonly used to treat viral influenza in China. There has been sufficient evidence that LHQW could effectively treat COVID-19. Nevertheless, the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds in LHQW are still vague. Methods: The compounds of LHQW and targets were collected from TCMSP, TCMID, Shanghai Institute of Organic Chemistry of CAS database, and relevant literature. Autodock Vina was used to carry out molecular docking. The pkCSM platform to predict the relevant parameters of compound absorption in vivo. The protein–protein interaction (PPI) network was constructed by the STRING database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out by Database for Annotation, Visualization, and Integrated Discovery (DAVID). The anti-(mutant) SARS-CoV-2 and anti-inflammation networks were constructed on the Cytoscape platform. Results: 280 compounds, 16 targets related to SARS-CoV-2, and 54 targets related to cytokine storm were obtained by screening. The key pathways Toll-like receptor signaling, NOD-like receptor signal pathway, and Jak-STAT signaling pathway, and the core targets IL6 were obtained by PPI network and KEGG pathway enrichment analysis. The network analysis predicted and discussed the 16 main anti-SARS-CoV-2 active compounds and 12 main anti-inflammation active compounds. Ochnaflavone and Hypericin are potential anti-mutant virus compounds in LHQW. Conclusions: In summary, this study explored the potential anti-(mutant) SARS-CoV-2 and anti-inflammation compounds of LHQW against COVID-19, which can provide new ideas and valuable references for discovering active compounds in the treatment of COVID-19.