Updated project metadata. The current SARS-CoV-2/COVID-19 pandemic causes medical and socioeconomic havoc. Despite the availability of vaccines, cost-effective treatment options preventing morbidity and mortality are urgently needed. To identify affordable, ubiquitously available, and effective treatments, we tested herbs consumed worldwide as herbal teas regarding their antiviral activity against SARS-CoV-2. Aqueous infusions prepared by boiling leaves of the Lamiaceae perilla and sage elicit potent and sustained antiviral activity against SARS-CoV-2 in therapeutic as well as prophylactic regimens. The herbal infusions exerted antiviral effects comparable to interferon-β and remdesivir but outperformed convalescent sera and interferon-α2 upon short-term treatment early after infection. Based on protein fractionation analyses, we identified caffeic acid, perilla aldehyde, and perilla alcohol as antiviral compounds. Global mass-spectrometry (MS) analyses performed comparatively in two different infection models (Vero E6 and Caco-2 cell lines) revealed changes of the proteome upon treatment with herbal infusions and provided insights into the mode of action. As inferred by the MS data, induction of heme oxygenase 1 (HMOX-1) was confirmed as effector mechanism by the antiviral activity of HMOX-1-inducing compounds sulforaphane and fraxetin. In conclusion, herbal teas based on perilla and sage exhibit antiviral activity against SARS-CoV-2 including the variants of concern Alpha, Beta, Delta, and Omicron.