The widespread surge in COVID-19 infections has caused an overwhelming rise in the number of hospital admissions and patient deaths. Massive research efforts are underway globally to develop COVID-19 vaccines. For the newly developed vaccines, given that safety beyond the trial population and the worldwide accessibility remains to be determined, there is also an opportunity to explore repurposing the pre-existing safe vaccines like the oral polio vaccine (OPV) leveraging their potential to provide cross-protection. The plausible mechanisms by which OPV might provide partial cross-immunity against SARS-CoV-2 include inhibition of PVR-TIGITCD226 axis and stimulation of trained innate immunity. Inhibition of PVR-TIGIT-CD226 axis by OPV unleashes the immunosuppressive effects of TIGIT, thus priming the immune system against the invading pathogen. Stimulation of trained innate immunity by OPV due to metabolic reprogramming and epigenetic modifications provides partial protection. This paper reviews the literature about live-attenuated OPV as a potential source of protection against COVID-19 and highlights the need for randomized, multicentric trials in India.