The available antiviral drugs against coronavirus disease 2019 (COVID-19) are limited. Oral drugs that can be prescribed to non-hospitalized patients are required. The 4′-fluoruridine, a nucleoside analog similar to remdesivir, is one of the promising candidates for COVID-19 oral therapy due to its ability to stall viral RdRp. Available data suggested that 4'-fluorouridine has antiviral activity against the respiratory syncytial virus, hepatitis C virus, lymphocytic choriomeningitis virus, and other RNA viruses, including SARS-CoV-2. In vivo study revealed that SARS-CoV-2 is highly susceptible to 4'-fluorouridine and was effective with a single daily dose versus molnupiravir administered twice daily. Although 4'-fluorouridine is considered as strong candidates, further studies are required to determine its efficacy in the patients and it’s genetic effects on humans. In this review, we the antiviral activity of 4′-fluorouridine is reviewed and compared it to other drugs currently in development. The current literature on 4′-fluorouridine's antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is compiled and discussed.