For individuals living with a chronic illness who require use of long-term medications, adherence is a vital aspect of successful symptom management and outcomes. This study investigated the effect of a smartphone app on adherence, self-efficacy, knowledge, and medication social support in a medically underserved adult population with various chronic illnesses. Participants were randomized to a group who used the app for one month or a control group provided with a printed medication list. Compared to the control group, participants receiving the intervention had significantly greater medication adherence (Cohen’s d = -0.52, p = .014) and medication self-efficacy (Cohen’s d = 0.43, p = .035). No significant effects were observed related to knowledge or social support. The findings suggest use of the app could positively impact chronic disease management in a medically underserved population in the United States.