The COVID-19 pandemic has caused havoc in the health sector. Inflammatory cytokines play an important role in the disease condition. Existing evidence has provided certain insights into the repurposing of the drugs. This meta-analysis and systematic review aimed to explore the efficacy of the administration of interferon beta-1b (IFN β-1b) and standard care versus only standard care as the therapeutic agent for managing COVID-19 patients who are severely ill. The search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, and Google Scholar, which were published during the period January 1, 2020, to February 16, 2023. All the included three studies were independently assessed for eligibility. The modified data extraction form of Cochrane were used. The quality of the three included studies was assessed using the Cochrane risk of bias tool. GradePro software was used to summarize the quality grading of the primary outcome measures. The time taken for clinical improvement was (MD: -3.28 days; 95% CI: -5.65, -0.91; P value = 0.007) when treated with IFN β-1b. The duration of hospital stays (MD: -2.43 days; 95% CI: -4.45, -0.30; P value = 0.03), and need for intensive care unit (ICU) admission (RR: 0.71; 95% CI: 0.52, 0.97; P value = 0.03) was statistically significant. Interferon beta-1b is proven to reduce the duration of hospital stay, and the improved clinical status may become a cornerstone of COVID-19 treatment.