OBJECTIVE: Persons with epilepsy (PWE), especially those with limited education backgrounds from developing countries, are challenged by complicated medication regimens, debilitating seizures, and stigmatization in their daily life. Consequently, it is difficult for physicians to ensure medication adherence. This study validates a novel mobile application which was hypothesized to increase medication adherence and self-management skills in PWE. Created by medical professionals, the application included behavioral and educational components and was built to be easy-to-understand for those of socio-economically disadvantaged backgrounds. METHODS: This was a parallel, two-armed randomized controlled trial in which a total of 96 participants were enrolled from a Neurology Outpatient Department into a control standard care group and a mobile application group that used the smartphone application (app) in addition to the standard medical treatment. The app was intuitive and easy to understand for those coming from a socio-economically disadvantaged background. Medication adherence and self-efficacy were assessed with the Morisky Green and Levine Scale (MGLS) and the Epilepsy Self Efficacy Scale (ESES). Patients were reassessed 12 weeks later. Change in seizure frequency following administration of the application was a secondary outcome. RESULTS: In an intent-to-treat analysis, the mobile application interventional group showed over a 60% increase in the proportion of medication adherence (P < 0.0001). The mean self-efficacy score for the mobile application group was increased from 269.5 to 289.75 (P < 0.0001). The control group showed no statistically significant increases in either the proportion adherent or mean self-efficacy scores. SIGNIFICANCE: This study demonstrated the statistically significant performance of a mobile application in improving medication adherence and self-management skills in Indian persons with epilepsy.