This comprehensive review explores the potential of using lactobacilli as a probiotic in the management of COVID-19. Our findings suggest that lactobacilli show promise in reducing the risk of death, gastrointestinal and overall symptoms, and respiratory failure, as well as in lowering cytokines and inflammatory markers associated with the disease. The molecular mechanisms by which lactobacilli protect against COVID-19 and other viral infections may be related to the reduction in inflammation, modulation of the immune response, and direct interaction with viruses to produce antiviral substances. However, the selected studies demonstrate the presence of mixed findings for various clinical, biochemical, hematological, and immunological parameters, which may be attributed to methodological differences among studies. We highlight the importance of clearly describing randomization processes to minimize bias and caution against small sample sizes and inappropriate statistical tests that could lead to errors. This review offers valuable insights into the therapeutic potential of lactobacilli in the context of COVID-19 and identifies avenues for further research and applications. These findings hold promise for the development of novel approaches to managing COVID-19 and warrant further investigation into the potential benefits of lactobacilli in combating the disease.