Background: Epilepsy requires continuous management and treatment to optimize patient outcomes. The advancement of digital health has led to the development of various mobile health (mHealth) tools designed to enhance treatment adherence among individuals with epilepsy. These solutions offer crucial support through features such as reminders, educational resources, personalized feedback, assistance with managing costs, shared decision-making, and access to supportive communities. To design effective medication adherence mHealth solutions, it is essential to evaluate the effectiveness of existing mHealth tools, understand the unique circumstances of different patients, and identify the roles of health care professionals within the digital care pathway. Existing studies on epilepsy primarily focus on self-management, whereas the effectiveness and usability of medical adherence mHealth solutions often remain overlooked. Furthermore, the involvement of health care professionals in digital care pathways for epilepsy as well as the impact of adherence mHealth solutions on the patient experience have not been adequately explored., Objective: This study aims to assess the effectiveness of current mHealth solutions designed to improve medical adherence among patients with epilepsy. Furthermore, the study will examine the experiences of patients using mHealth solutions for maintaining medical adherence in epilepsy care. Finally, this review intends to determine the roles of health care professionals within mHealth systems aimed at supporting adherence to medication among patients with epilepsy., Methods: A systematic literature review has been selected as the appropriate method to address the research questions, adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The inclusion and exclusion criteria have been carefully selected, and both qualitative and quantitative analyses will be used to analyze the results. The expected results will mainly focus on the comparison, classification, and analysis of the effectiveness of current medical adherence mHealth tools. Moreover, the patient experiences using available medical adherence mHealth tools for epilepsy will be assessed. Finally, the role of health care professionals in the epilepsy digital care pathway will be explored, with emphasis on medical adherence., Results: The initial search, full-text screening, and data extraction have been carried out. Thirty-three papers were included in the final stage of the review. The study is expected to be completed by October 2024., Conclusions: To enhance the digital care pathway for epilepsy, a medical adherence mHealth solution should be personalized, manage medications, include an alarm system, track seizures, support consultations, and offer updated treatment plans. This study aims to understand how findings from the research questions can improve mHealth solutions for individuals with epilepsy. Insights from this research on the effectiveness of current mHealth adherence solutions will provide guidance for developing future mHealth systems, making them more efficient and effective in managing epilepsy., Trial Registration: PROSPERO CRD4202347400; https://tinyurl.com/48mfx22e., International Registered Report Identifier (irrid): DERR1-10.2196/55123., (©Pantea Keikhosrokiani, Manria Polus, Sharon Guardado Medina, Minna Isomursu. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.08.2024.)