The anti-COVID-19 effects and mechanisms of Artemisia and its constituents include, but are not limited to: (1) inhibiting SARS-CoV-2 invasion and replication by targeting the key proteins of spike, ACE2, spike–ACE2 interaction, TMPRSS2, and NSPS, including Mpro, PLpro, and RdRp; (2) regulating immune and inflammatory responses by targeting inflammatory cytokines and chemokines; (3) protecting against ARDS and MODS by suppressing the crosstalk of viral toxicity, endothelial damage, and cytokine storm. The gene discussed is TMPRSS2; the disease is COVID-19.