Dysbiosis of the human gut microbiome has been linked to various health conditions, including respiratory tract infections (RTIs) through the gut-lung axis. Several trials have reported that synbiotic therapy could help prevent RTIs or relieve symptoms of some diseases. This meta-analysis comprehensively evaluates the clinical effects of synbiotic supplements for preventing RTIs. PubMed and Google Scholar were searched by keywords for eligible clinical trials until April 2019. Sixty-two studies were retrieved, and 16 studies were selected for meta-analysis. The primary outcomes were defined as the proportion of participants with RTIs at least once or the times of RTI episodes during follow-up based on the intention-to-treat approach. Overall, synbiotic interventions reduced the incidence rate of RTIs by 16% (95% CI: 4%, 27%) and the proportion of participants experiencing RTIs by 16% (95% CI: 5%, 26%). There was no significant evidence of publication bias. A subgroup analysis suggested more prominent effects of synbiotics among adults than infants and children for RTI prevention. The sensitivity analysis excluding trials with prebiotics or probiotics as controls was consistent with our primary analysis. This meta-analysis of clinical trials involving >10,000 individuals showed that synbiotic interventions could be an alternative nutrition strategy for conferring human health and preventing RTIs. Future investigations on the clinical efficacy and safety of synbiotic interventions are warranted with strain-specific and dose-specific approaches.