BACKGROUND: Medication non-adherence remains a major barrier to effective chronic disease management, particularly in low- and middle-income countries. In Ghana, limited access to continuous care and patient engagement tools contributes to poor adherence among individuals living with type 2 diabetes and hypertension. Mobile health interventions, including smartphone applications, may offer scalable solutions to support long-term medication use and self-management. Here, we assess the effect of a smartphone-based intervention on medication adherence among adults with these conditions. METHODS: We conducted a quasi-experimental study among 874 adults with type 2 diabetes or hypertension in Ghana. Participants were assigned to either a smartphone-based intervention, which included medication reminders, educational content, and self-monitoring tools, or standard care involving routine outpatient management and follow-up without access to the smartphone-based intervention. We measured medication adherence at baseline and six months using the Medication Adherence Rating Scale and assessed it through generalised estimating equations and difference-in-differences analyses, adjusting for baseline adherence, age, sex, and treatment setting. RESULTS: Use of the smartphone application was associated with a greater improvement in medication adherence over six months in the overall study population (adjusted beta coefficient (aβ) = 0.062; 95% confidence interval (CI) = 0.010-0.123). Similar improvements were observed among participants with type 2 diabetes (aβ = 0.067; 95% CI = 0.012-0.135) and hypertension (aβ = 0.068; 95% CI = 0.005-0.134). However, there was no statistically significant difference in adherence between the intervention and control groups at six months. CONCLUSIONS: Smartphone-based interventions were associated with modest improvements in medication adherence over time, although between-group differences at follow-up were not statistically significant. As access to mobile technology expands across Africa, such interventions may provide scalable strategies to support chronic disease management.