Background: Telemedicine is defined by three characteristics: (1) using information and communication technologies, (2) covering a geographical distance, and (3) involving professionals who deliver care directly to a patient or a group of patients. It is said to improve chronic care management and self-management in patients with chronic diseases. However, currently available guidelines for the care of patients with diabetes, hypertension, or dyslipidemia do not include evidence-based guidance on which components of telemedicine are most effective for which patient populations.Objective: The primary aim of this study was to identify, synthesize, and critically appraise evidence on the effectiveness of telemedicine solutions and their components on clinical outcomes in patients with diabetes, hypertension, or dyslipidemia.Methods: We conducted an umbrella review of high-level evidence, including systematic reviews and meta-analyses of randomized controlled trials. On the basis of predefined eligibility criteria, extensive automated and manual searches of the databases PubMed, EMBASE, and Cochrane Library were conducted. Two authors independently screened the studies, extracted data, and carried out the quality assessments. Extracted data were presented according to intervention components and patient characteristics using defined thresholds of clinical relevance. Overall certainty of outcomes was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.Results: Overall, 3564 references were identified, of which 46 records were included after applying eligibility criteria. The majority of included studies were published after 2015. Significant and clinically relevant reduction rates for glycated hemoglobin (HbA(1c);<=-0.5%) were found in patients with diabetes. Higher reduction rates were found for recently diagnosed patients and those with higher baseline HbA(1c) (>8%). Telemedicine was not found to have a significant and clinically meaningful impact on blood pressure. Only reviews or meta-analyses reporting lipid outcomes in patients with diabetes were found. GRADE assessment revealed that the overall quality of the evidence was low to very low.Conclusions: The results of this umbrella review indicate that telemedicine has the potential to improve clinical outcomes in patients with diabetes. Although subgroup-specific effectiveness rates favoring certain intervention and population characteristics were found, the low GRADE ratings indicate that evidence can be considered as limited. Future updates of clinical care and practice guidelines should carefully assess the methodological quality of studies and the overall certainty of subgroup-specific outcomes before recommending telemedicine interventions for certain patient populations.