The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that struck in late 2019 and early 2020 is a serious threat to human health. Since there are no approved drugs that satisfactorily treat this condition, all efforts at drug design and/or clinical trials are warranted and reasonable. Drug repurposing is a well-known strategy that seeks to deploy existing licensed drugs for newer indications and that provides the quickest possible transition from the bench to the bedside to meet therapeutic needs. At present, several existing licensed drugs such as chloroquine, hydroxychloroquine, methylprednisolone, dexamethasone, and remdesivir have been used because of their potential efficacy in inhibiting COVID-19. Recently, antibiotics such as tetracyclines and macrolides have been reported to be effective against COVID-19. A combination of tetracyclines and macrolides may be a potential treatment for COVID-19 because there are some differences in the mechanism of action of tetracyclines and macrolides.