Probiotics have been hypothesized to play a beneficial role in modulating immune responses and gut microbiota in various clinical settings. This systematic review and meta-analysis aimed to assess the effectiveness of probiotics in reducing all-cause mortality among patients diagnosed with COVID-19. We conducted a comprehensive search of the following databases: PubMed, Scopus, and Web of Science for published studies, and medRxiv, Research Square, and SSRN for preprints. The search spanned from the inception of these databases to April 4, 2023. We included studies that investigated the use of probiotics as an intervention and their impact on all-cause mortality in patients with COVID-19. A random-effects model meta-analysis was employed to estimate the pooled odds ratio, along with 95% confidence interval, to quantify the outcomes associated with probiotic use compared to other interventions. Our systematic review comprised six studies, encompassing a total of 642 patients. The meta-analysis, employing a random-effects model, demonstrated a statistically significant reduction in the risk of all-cause mortality when probiotics were administered to patients with COVID-19, compared to those not receiving probiotics (pooled odds ratio = 0.44; 95% confidence interval 0.24–0.82). In conclusion, evidence derived from randomized controlled trials (RCTs) indicates a survival benefit associated with the use of probiotics among COVID-19 patients. However, it is essential to exercise caution and await data from large-scale randomized trials to definitively confirm the mortality benefits of probiotics in this patient population.