Objectives We aimed to evaluate the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) and incidence of various respiratory and infectious diseases and site-specific fractures. Methods Large randomized controlled trials (RCTs) of SGLT2is enrolling more than 400 subjects were included. Outcomes of interest were various serious adverse events regarding to respiratory and infectious disorders and site-specific fractures. Meta-analysis was done using risk ratio (RR) and 95% confidence interval (CI) as effect size. Results Thirty-two large RCTs were included in this meta-analysis. Use of SGLT2is was significantly associated with the lower incidences of 6 kinds of noninfectious respiratory diseases {e.g., Asthma (RR 0.64, 95% CI 0.43–0.96; P  = 0.0299), Chronic obstructive pulmonary disease COPD (RR 0.75, 95% CI 0.62–0.91; P  = 0.0027), and Respiratory failure (RR 0.78, 95% CI 0.61–0.99; P  = 0.0447)} and 4 kinds of infectious respiratory diseases {e.g., Bronchitis (RR 0.61, 95% CI 0.46–0.81; P  = 0.0007), and Pneumonia (RR 0.85, 95% CI 0.78–0.93; P  = 0.0002)}. Use of SGLT2is was not significantly associated with the incidences of 31 kinds of site-specific fractures (e.g., Hip fracture, Femoral neck fracture, and Spinal fracture; P  > 0.05). Conclusions Our meta-analysis confirmed the benefits of SGLT2is against 6 kinds of noninfectious respiratory diseases (e.g., Asthma, COPD, and Respiratory failure) and 4 kinds of infectious respiratory diseases (e.g., Bronchitis, and Pneumonia). These findings suggest a likelihood that SGLT2is might be used to prevent or treat these respiratory diseases. Moreover, our meta-analysis for the first time revealed no association between use of SGLT2is and incidence of various site-specific fractures.