BACKGROUND: The high rate of transmission and infection of coronavirus disease 2019 (COVID-19) is a public health emergency of major epidemiological concern. No definitive treatments have been established, and vaccinations have only recently begun. We aim to review the efficacy and safety of Interferon Beta (IFN-beta) in patients who have a confirmed COVID-19 diagnosis. MATERIALS AND METHODS: A search from PubMed, Science Direct, Cochrane, and Clinicaltrials.gov databases were conducted from December 2019 to December 2020 to review the efficacy and safety of IFN-beta in adult patients with COVID-19 confirmed. We included randomized controlled trials, case reports, and experimental studies. Correspondences, letters, editorials, reviews, commentaries, case control, cross-sectional, and cohort studies that did not include any new clinical data were excluded. RESULTS: Of the 66 searched studies, 8 were included in our review. These studies demonstrated that although IFN-beta did not reduce the time to clinical response, there was an increase in discharge rate at day 14 and a decrease in mortality at day 28. The time to negative reverse transcription polymerase chain reaction (RT-PCR) was shown to be significantly shortened in patients receiving IFN-beta, along with a lower nasopharyngeal viral load. Further, patients receiving IFN-beta had a less significant rise in IL-6. IFN-beta was shown to decrease intensive care unit (ICU) admission rate, the requirement of invasive ventilation in severe cases, and improve the survival rate compared to control groups. There were no severe adverse events reported. Our review found that patients who received early treatment with IFN-beta experienced significantly reduced length of hospitalization, mortality, ICU admission, and mechanical ventilation. A greater chance of clinical improvement and improved imaging studies was noted in patients who received IFN-beta. There were no reported deaths associated with the addition of IFN-beta. Further randomized trials involving more significant sample sizes are needed to better understand the effect of IFN-beta on survival in COVID-19. CONCLUSION: This review identified encouraging data and outcomes of incorporating IFN-beta to treat COVID-19 patients. IFN-beta has been shown to decrease hospital stay's overall length and decrease the severity of respiratory symptoms when added to the standard of care. Also, in some studies, it has been demonstrated to reduce the length of ICU stay, enhance survival rate, and decrease the need for invasive mechanical ventilation. There were minor side effects reported (neuropsychiatric symptoms and hypersensitivity reaction). However, randomized clinical trials with a large sample size are needed to assess IFN-beta's benefit precisely.