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Background: Digital health interventions (DHIs) have rapidly evolved and significantly revolutionized the health care system. The quadruple aims of health care (improving population health, enhancing consumer experience, enhancing health care provider [HCP] experience, and decreasing health costs) serve as a strategic guiding framework for DHIs. It is unknown how DHIs can impact the burden of type 2 diabetes mellitus (T2DM), as measured by the quadruple aims. Objective: This study aimed to systematically review the effects of DHIs on improving the burden of T2DM, as measured by the quadruple aims. Methods: PubMed, Embase, CINAHL, and Web of Science were searched for studies published from January 2014 to March 2024. Primary outcomes were the development of T2DM, hemoglobin A_1c (HbA_1c) change, and blood glucose change (dysglycemia changes). Secondary outcomes were consumer experience, HCP experience, and health care costs. Outcomes were mapped to the quadruple aims. DHIs were categorized using the World Health Organization’s DHI classification. For each study, DHI categories were assessed for their effects on each outcome, categorizing the effects as positive, negative, or neutral. The overall effects of each DHI category were determined by synthesizing all reported positive, neutral, or negative effects regardless of the number of studies supporting each effect. The Cochrane risk-of-bias version 2 (RoB 2) tool for randomized trials was used to assess the quality of randomized controlled trials (RCTs), while the ROBINS-I (risk of bias in nonrandomized studies of interventions) tool was applied for nonrandomized studies. Results: In total, 53 papers were included. For the T2DM development outcome, the effects of DHIs were positive in 1 (1.9%) study and neutral in 9 (17%) studies, and there were insufficient data to assess in 4 (7.5%) studies. For the dysglycemia outcome, the effects were positive in 23 (43.4%) studies and neutral in 24 (45.3%) studies, and there were insufficient data in 6 (11.3%) studies. There were mixed effects on consumer experience (n=13, 24.5%) and a lack of studies reporting HCP experience (n=1, 1.9%) and health care costs (n=3, 5.7%). All studies that reported positive population health outcomes used a minimum of 2 distinct categories of DHIs. Among these successful studies, the one that reported delaying the development of T2DM and 16 (69.6%) of those reporting improvements in dysglycemia involved HCP interaction. Targeted communication with persons (TCP), personal health tracking (PHT), and telemedicine (TM) showed some evidence as a potentially useful tool for T2DM prevention and dysglycemia. Conclusions: The effects of DHIs on T2DM prevention, as measured by the quadruple aims, have not been comprehensively assessed, with proven benefits for population health, mixed results for consumer experience, and insufficient studies on HCP experience and health care costs. To maximize their effectiveness in preventing T2DM and managing dysglycemia, DHIs should be used in combination and strategically integrated with in-person or remote HCP interaction. Trial Registration: PROSPERO CRD42024512690; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024512690