Primary healthcare facilities in Indonesia face persistent challenges in managing type 2 diabetes and hypertension, largely due to suboptimal medication adherence and limited telepharmacy integration. This mixed-methods quasi-experimental study evaluated a multicomponent telepharmacy intervention across ten community health centers in Depok. Using stratified random sampling, 424 chronic patients were assigned to intervention or control groups. Grounded in the Health Belief Model and Technology Acceptance Model, the intervention combined the “FarmasiKronis Depok” application with twelve virtual pharmacist consultations. Outcomes were assessed using MMAS-8, SF-36, and eHEALS. Quantitative data were analyzed via ANCOVA and multivariate regression, supplemented by thematic analysis of 45 semi-structured interviews. The intervention significantly improved medication adherence (+2.1 points; d = 1.52; p < 0.001) and quality of life (+19.2 points; d = 1.42; p < 0.001) compared with controls. Regression identified intervention exposure (β = 1.42) and digital health literacy (β = 0.12) as primary predictors. Qualitative themes highlighted digital accessibility (71%), academic institutional support (62%), and persistent digital literacy barriers (40%). Notably, university-educated participants achieved an 85% high-adherence rate. Pharmacist-led digital transformation substantially optimizes chronic disease management in primary care. Strategic integration with national health platforms, standardized telepharmacy reimbursement, and expanded digital competency training offer scalable pathways to reduce hospital readmissions by 28% and enhance health system sustainability