This current meta-analysis review was conducted to examine the effectiveness of Qigong-based therapy on individuals with major depressive disorder. Six electronic databases (PubMed, PsycINFO, Cochrane Library, and Web of Science, Chinese National Knowledge Infrastructure, and Wangfang) were employed to retrieve potential articles that were randomized controlled trials. The synthesized effect sizes (Hedges’ g) were computerized to explore the effectiveness of Qigong-based therapy. Additionally, a moderator analysis was performed based on the control type. The pooled results indicated that Qigong-based therapy has a significant benefit on depression severity (Hedges’ g = −0.64, 95% CI −0.92 to −0.35, p < 0. 001, I= 41.73%). Specifically, Qigong led to significantly reduced depression as compared to the active control groups (Hedges’ g = −0.47, 95% CI −0.81 to −0.12, p = 0.01, I= 22.75%) and the passive control groups (Hedges’ g = −0.80, 95% CI −1.23 to −0.37, p < 0.01, I= 48.07%), respectively. For studies which reported categorical outcomes, Qigong intervention showed significantly improved treatment response rates (OR = 4.38, 95% CI 1.26 to 15.23, p = 0.02) and remission rates (OR = 8.52, 95% CI 1.91 to 37.98, p = 0.005) in comparison to the waitlist control group. Conclusions: Qigong-based exercises may be effective for alleviating depression symptoms in individuals with major depressive disorder. Future well-designed, randomized, controlled trials with large sample sizes are needed to confirm these findings.