BACKGROUND: Depression is underdiagnosed and undertreated in primary health care. When associated with chronic physical disorders, it worsens outcomes. There is a clear gap in the treatment of depression in low- and middle-income countries (LMICs), where specialists and funds are scarce. Interventions supported by mobile health (mHealth) technologies may help to reduce this gap. Mobile phones are widely used in LMICs, offering potentially feasible and affordable alternatives for the management of depression among individuals with chronic disorders. OBJECTIVE: This study aimed to explore the potential effectiveness of an mHealth intervention to help people with depressive symptoms and comorbid hypertension or diabetes and explore the feasibility of conducting large randomized controlled trials (RCTs). METHODS: Emotional Control (CONEMO) is a low-intensity psychoeducational 6-week intervention delivered via mobile phones and assisted by a nurse for reducing depressive symptoms among individuals with diabetes or hypertension. CONEMO was tested in 3 pilot studies, 1 in Sao Paulo, Brazil, and 2 in Lima, Peru. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) at enrollment and at 6-week follow-up. RESULTS: The 3 pilot studies included a total of 66 people. Most participants were females aged between 41 and 60 years. There was a reduction in depressive symptoms as measured by PHQ-9 in all pilot studies. In total, 58% (38/66) of the participants reached treatment success rate (PHQ-9 <10), with 62% (13/21) from Sao Paulo, 62% (13/21) from the first Lima pilot, and 50% (12/24) from the second Lima pilot study. The intervention, the app, and the support offered by the nurse and nurse assistants were well received by participants in both settings. CONCLUSIONS: The intervention was feasible in both settings. Clinical data suggested that CONEMO may help in decreasing participants' depressive symptoms. The findings also indicated that it was possible to conduct RCTs in these settings.