Severe acute respiratory syndrome coronavirus 2 principally weakens the hosts’ innate immune system by impairing the interferon function and production. Type I interferons (IFNs) especially IFN-β are best known for their antiviral activities. IFNs accompanied by the standard care protocols have opened up unique opportunities for treating the coronavirus disease 2019 (COVID-19). The databases including PubMed, SCOPUS, EMBASE, and Google Scholar were searched up to October 30, 2020. The primary and secondary outcomes were considered discharge and mortality, respectively. The abovementioned outcomes of standard care protocol were compared with the standard care plus IFN-β in the confirmed COVID-19 patients. Out of 356 records identified, 12 randomized clinical trial studies were selected for full-text screening. Finally, 5 papers were included in the systematic review and 3 papers in the meta-analysis. The average mortality rate was reported as 6.195% and 18.02% in intervention and control groups, respectively. Likewise, the median days of hospitalization were lower in the intervention group (9 days) than the control group (12.25 days). According to meta-analysis, IFN-β was found to increase the overall discharge rate (RR = 3.05; 95% CI: 1.09–5.01). Our findings revealed that early administration of IFN-β in combination with antiviral drugs is a promising therapeutic strategy against COVID-19.