BACKGROUND: With the exponential increase in mobile phone users in India, a large number of public health initiatives are leveraging information technology and mobile devices for health care delivery. Given the considerable financial and human resources being invested in these initiatives, it is important to ascertain their role in strengthening health care systems. OBJECTIVE: We undertook this review to identify the published mobile health (mHealth) or telemedicine initiatives in India in terms of their current role in health systems strengthening. The review classifies these initiatives based on the disease areas, geographical distribution, and target users and assesses the quality of the available literature. METHODS: A search of the literature was done to identify mHealth or telemedicine articles published between January 1997 and June 2017 from India. The electronic bibliographic databases and registries searched included MEDLINE, EMBASE, Joanna Briggs Institute Database, and Clinical Trial Registry of India. The World Health Organization health system building block framework was used to categorize the published initiatives as per their role in the health system. Quality assessment of the selected articles was done using the Cochrane risk of bias assessment and National Institutes of Health, US tools. RESULTS: The combined search strategies yielded 2150 citations out of which 318 articles were included (primary research articles=125; reviews and system architectural, case studies, and opinion articles=193). A sharp increase was seen after 2012, driven primarily by noncommunicable disease-focused articles. Majority of the primary studies had their sites in the south Indian states, with no published articles from Jammu and Kashmir and north-eastern parts of India. Service delivery was the primary focus of 57.6% (72/125) of the selected articles. A majority of these articles had their focus on 1 (36.0%, 45/125) or 2 (45.6%, 57/125) domains of health system, most frequently service delivery and health workforce. Initiatives commonly used client education as a tool for improving the health system. More than 91.2% (114/125) of the studies, which lacked a sample size justification, had used convenience sampling. Methodological rigor of the selected trials (n=11) was assessed to be poor as majority of the studies had a high risk for bias in at least 2 categories. CONCLUSIONS: In conclusion, mHealth initiatives are being increasingly tested to improve health care delivery in India. Our review highlights the poor quality of the current evidence base and an urgent need for focused research aimed at generating high-quality evidence on the efficacy, user acceptability, and cost-effectiveness of mHealth interventions aimed toward health systems strengthening. A pragmatic approach would be to include an implementation research component into the existing and proposed digital health initiatives to support the generation of evidence for health systems strengthening on strategically important outcomes.