BACKGROUND: Major depressive disorder (MDD) accounts for 40.5% of disability-adjusted life years caused by mental and substance use disorders. Barriers such as stigma and financial and physical access to care have been reported, highlighting the need for innovative, accessible, and cost-effective psychological interventions. The effectiveness of supportive SMS text messaging in alleviating depression symptoms has been proven in clinical trials, but this approach can only help those with mobile phones. OBJECTIVE: This paper presents the protocol for a study that will aim to evaluate the feasibility, comparative effectiveness, and user satisfaction of daily supportive email messaging as an effective strategy compared to daily supportive text messaging as part of the treatment of patients with MDD. METHODS: This trial will be carried out using a hybrid type II implementation-effectiveness design. This design evaluates the effectiveness of an implementation strategy or intervention, while also evaluating the implementation context associated with the intervention. Patients with MDD receiving usual care will be randomized to receive either daily supportive email messaging or daily supportive text messaging of the same content for 6 months. The Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, and the 5-item World Health Organization Well-Being Index will be used to evaluate the effectiveness of both strategies. The implementation evaluation will be guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, as well as the Consolidated Framework for Implementation Research. All outcome measures will be analyzed using descriptive and inferential statistics. Qualitative data will be analyzed using thematic analysis. RESULTS: Data collection for this trial began in April 2021. We expect the study results to be available within 18 months of study commencement. The results will shed light on the feasibility, acceptability, and effectiveness of using automated emails as a strategy for delivering supportive messages to patients with MDD in comparison to text messaging. CONCLUSIONS: The outcome of this trial will have translational impact on routine patient care and access to mental health, as well as potentially support mental health policy decision-making for health care resource allocation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04638231; https://clinicaltrials.gov/ct2/show/NCT04638231. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29495.