Background In many low- and middle-income countries (LMICs), heart disease and stroke are the leading causes of death as cardiovascular risk factors such as diabetes and hypertension rapidly increase. The Cambodian nongovernmental organization, MoPoTsyo, trains local residents with diabetes to be peer educators (PEs) to deliver chronic disease self-management training and medications to 14,000 people with hypertension and/or diabetes in Cambodia. We collaborated with MoPoTsyo to develop a mobile-based messaging intervention (mobile health; mHealth) to link MoPoTsyo’s database, PEs, pharmacies, clinics, and people living with diabetes and/or hypertension to improve adherence to evidence-based treatment guidelines. Objective This study aimed to understand the facilitators and barriers to chronic disease management and the acceptability, appropriateness, and feasibility of mHealth to support chronic disease management and strengthen community-clinical linkages to existing services. Methods We conducted an exploratory qualitative study using semistructured interviews and focus groups with PEs and people living with diabetes and/or hypertension. Interviews were recorded and conducted in Khmer script, transcribed and translated into the English language, and uploaded into Atlas.ti for analysis. We used a thematic analysis to identify key facilitators and barriers to disease management and opportunities for mHealth content and format. The information-motivation-behavioral model was used to guide data collection, analysis, and message development. Results We conducted six focus groups (N=59) and 11 interviews in one urban municipality and five rural operating districts from three provinces in October 2016. PE network participants desired mHealth to address barriers to chronic disease management through reminders about medications, laboratory tests and doctor’s consultations, education on how to incorporate self-management into their daily lives, and support for obstacles to disease management. Participants preferred mobile-based voice messages to arrive at dinnertime for improved phone access and family support. They desired voice messages over texts to communicate trust and increase accessibility for persons with limited literacy, vision, and smartphone access. PEs shared similar views and perceived mHealth as acceptable and feasible for supporting their work. We developed 34 educational, supportive, and reminder mHealth messages based on these findings. Conclusions These mHealth messages are currently being tested in a cluster randomized controlled trial (#1R21TW010160) to improve diabetes and hypertension control in Cambodia. This study has implications for practice and policies in Cambodia and other LMICs and low-resource US settings that are working to engage PEs and build community-clinical linkages to facilitate chronic disease management.