BACKGROUND: Informal caregivers (ie, individuals who provide assistance to a known person with health or functional needs, often unpaid) experience high levels of stress. Caregiver stress is associated with negative outcomes for both caregivers and care recipients. Mindfulness-based interventions (MBIs) show promise for improving stress, emotional distress, and sleep disturbance in caregivers of persons with Alzheimer disease and related dementias (ADRD). Commercially available mobile mindfulness apps can deliver MBIs to caregivers of persons with ADRD in a feasible and cost-effective manner. OBJECTIVE: We are conducting a single-blind feasibility proof-of-concept randomized controlled trial (RCT; National Institutes of Health [NIH] stage 1B) comparing 2 free mobile apps: the active intervention Healthy Minds Program (HMP) with within-app text tailored for addressing stress among caregivers of persons with ADRD, versus Wellness App (WA), a time- and dose-matched educational control also tailored for caregivers of persons with ADRD. METHODS: We aim to recruit 80 geographically diverse and stressed caregivers of persons with ADRD. Interested caregivers use a link or QR code on a recruitment flyer to complete a web-based eligibility screener. Research assistants conduct enrollment phone calls, during which participants provide informed consent digitally. After participants complete baseline surveys, we randomize them to the mindfulness-based intervention (HMP) or educational control podcast app (WA) and instruct them to listen to prescribed content for 10 minutes per day (70 minutes per week) for 12 weeks. Caregivers are blinded to intervention versus control. The study team checks adherence weekly and contacts participants to promote adherence as needed. Participants complete web-based self-report measures at baseline, posttest, and follow-up; weekly process measures are also completed. Primary outcomes are a priori set feasibility benchmarks. Secondary outcomes are stress, emotional distress, sleep disturbance, caregiver burden, mindfulness, awareness, connection, insight, and purpose. We will calculate 1-sided 95% CI to assess feasibility benchmarks. Effect sizes of change in outcomes will be used to examine the proof of concept. RESULTS: Recruitment started on February 20, 2023. We have enrolled 27 caregivers (HMP: n=14; WA: n=13) as of June 2023. Funding began in August 2022, and we plan to finish enrollment by December 2023. Data analysis is expected to begin in May 2024 when all follow-ups are complete; publication of findings will follow. CONCLUSIONS: Through this trial, we aim to establish feasibility benchmarks for HMP and WA, as well as establish a proof of concept that HMP improves stress (primary quantitative outcome), emotional distress, sleep, and mindfulness more than WA. Results will inform a future efficacy trial (NIH stage II). HMP has the potential to be a cost-effective solution to reduce stress in caregivers of persons with ADRD, benefiting caregiver health and quality of care as well as patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05732038; https://clinicaltrials.gov/study/NCT05732038. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50108.