Background: Mental health problems among workers are a significant global concern, leading to substantial economic losses, particularly due to presenteeism. While mindfulness and self-compassion practices have shown promise in improving psychological well-being and occupational outcomes, traditional interventions often require a high time commitment. Low-intensity digital interventions remain underexplored, especially in the context of occupational health. Objective: This study aimed to develop and evaluate the effectiveness of a smartphone-based self-care app that enables independent practice of mindfulness and self-compassion without facilitator support. Specifically, it assessed the effects of self-compassion meditation (SCM) and mindfulness meditation (MM) on mental health and work-related outcomes among nonclinical Japanese workers. Methods: This open-label, 3-arm randomized controlled trial recruited 300 working adults in Japan, who were randomly assigned to SCM (n=101), MM (n=100), or a waitlist control group (n=99). Participants in the SCM and MM groups engaged in daily guided meditation via a custom-built smartphone app over 4 weeks. Primary outcomes included psychological distress (Kessler Psychological Distress Scale-6) and work performance (World Health Organization Health and Work Performance Questionnaire and the Stanford Presenteeism Scale), while secondary outcomes encompassed cognitive flexibility, self-compassion, perceived stress, work engagement, psychological safety, and self-perceived creativity. Assessments were conducted at baseline, postintervention (4 wk), and 1-month follow-up (8 wk). Recruitment occurred in 2 waves (November 2022-December 2022 and June 2023), with follow-up assessments completed by September 2023. Results: A total of 300 participants (mean age of 35.44, SD 9.14 y; n=180, 60% female) were randomized. Adherence was high in both intervention groups (mean completed days: SCM 23.30, SD 5.58; MM 22.95, SD 6.25), with an overall dropout rate of 21.4%. No significant group × time interactions were detected for most outcomes, although significant main effects of time were observed for several measures, including work performance and self-compassion, with small effect sizes. Within-group analyses suggested broader improvements in the SCM group, whereas changes in the MM group were more limited. In sensitivity analyses using linear mixed-effects models, a significant group × time interaction was detected for work performance, with a larger pre-post improvement in SCM. Conclusions: This low-intensity, fully self-guided, smartphone-based meditation program demonstrated good feasibility, as reflected by high adherence and relatively low attrition. Between-group effects were limited; therefore, the findings should be interpreted as preliminary and do not support strong causal claims of intervention superiority. Clinical significance remains unclear in this nonclinical sample and should be evaluated in future studies. Trial Registration: UMIN-CTR UMIN000049466; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000056324 International Registered Report Identifier (IRRID): RR2-10.2196/53541 Introduction Mental health problems among workers pose a critical challenge with far-reaching implications for the global economy. According to the World Health Organization (WHO), depression and anxiety disorders account for the loss of approximatel... [44397 chars]