BACKGROUND: Previous systematic reviews have aimed to clarify the effect of telemedicine on diabetes. However, such reviews often have a narrow focus, which calls for a more comprehensive systematic review within the field. Hence, the objective of the present systematic review, meta-analysis, and meta-regression is to evaluate the effectiveness of telemedicine solutions versus any comparator without the use of telemedicine on diabetes-related outcomes among adult patients with type 2 diabetes (T2D). METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We considered telemedicine randomized controlled trials (RCT) including adults (≥18 years) diagnosed with T2D. Change in glycated hemoglobin (HbA1c, %) was the primary outcome. PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) were searched on October 14, 2020. An overall treatment effect was estimated using a meta-analysis performed on the pool of included studies based on the mean difference (MD). The revised Cochrane risk-of-bias tool was applied and the certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: The final sample of papers included a total of 246, of which 168 had sufficient information to calculate the effect of HbA1c%. The results favored telemedicine, with an MD of -0.415% (95% confidence interval [CI] = -0.482% to -0.348%). The heterogeneity was great (I2 = 93.05%). A monitoring component gave rise to the higher effects of telemedicine. CONCLUSIONS: In conclusion, telemedicine may serve as a valuable supplement to usual care for patients with T2D. The inclusion of a telemonitoring component seems to increase the effect of telemedicine.