BACKGROUND: Depression is a disorder characterized by significant and persistent depressed mood, cognitive impairment, impaired voluntary activity, working memory, and somatic symptoms. AIM: To determine the efficacy of Qi-based mindfulness therapy (QMT) in treating anxiety, depression, and sleep disturbances in individuals with mild-to-moderate depression. METHODS: A self-controlled before-after trial was conducted. The study invited online participants for recruitment between May and July 2023. Participants (n = 18) aged 18-65 years with mild-to-moderate depression, who were receiving QMT training for 4 weeks, were included. The primary efficacy indicators were the 17 Hamilton Depression Rating Scale and Hamilton Anxiety Scale scores. The secondary outcome indicators included the Zung Self-rating Depression Scale, the self-rating Anxiety Scale, and the Insomnia Severity Index. Pre- and post-intervention assessments were conducted. The patients' symptoms related to depression, anxiety, and insomnia were reassessed 4 weeks after the post-intervention evaluation. RESULTS: Patients who underwent the QMT intervention for 4 weeks exhibited a statistically significant reduction in scores on the 17 Hamilton Depression Rating Scale, Hamilton Anxiety Scale, the Zung Self-Rating Depression Scale, the Self-Rating Anxiety Scale, and the Insomnia Severity Index relative to their pre-intervention scores (all P < 0.05). CONCLUSION: QMT training for 4 weeks is an effective nonpharmacological treatment for symptoms of depression, anxiety, and insomnia among patients with mild-to-moderate depression.