BACKGROUND: Despite potential for benefit, mindfulness remains an emergent area in perinatal mental health care, and evidence of smartphone-based mindfulness training for perinatal depression is especially limited. OBJECTIVE: The objective of this study was to evaluate the effectiveness of a smartphone-based mindfulness training intervention during pregnancy on perinatal depression and other mental health problems with a randomized controlled design. METHODS: Pregnant adult women who were potentially at risk of perinatal depression were recruited from an obstetrics clinic and randomized to a self-guided 8-week smartphone-based mindfulness training during pregnancy group or attention control group. Mental health indicators were surveyed over five time points through the postpartum period by online self-assessment. The assessor who collected the follow-up data was blind to the assignment. The primary outcome was depression as measured by symptoms, and secondary outcomes were anxiety, stress, affect, sleep, fatigue, memory, and fear. RESULTS: A total of 168 participants were randomly allocated to the mindfulness training (n=84) or attention control (n=84) group. The overall dropout rate was 34.5%, and 52.4% of the participants completed the intervention. Mindfulness training participants reported significant improvement of depression (group × time interaction χ CONCLUSIONS: Smartphone-based mindfulness training is an effective intervention in improving maternal perinatal depression for those who are potentially at risk of perinatal depression in early pregnancy. Nulliparous women are a promising subgroup who may benefit more from mindfulness training. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900028521; http://www.chictr.org.cn/showproj.aspx?proj=33474.