Major depressive disorder (MDD) causes a persistent feeling of sadness and loss of interest. It can lead to emotional and physical problems. Treatments such as antidepressant and cognitive behavioral therapy for MDD have many limitations. Traditional East Asian Herbal Medicine (TEAM) is a representative modality of Complementary and Integrative Medicine (CIM) which can be used for MDD. However, no study has systematically reviewed the efficacy or safety of TEAM for MDD so far. Therefore, we performed a systematic review and meta-analysis to evaluate effectiveness and safety of TEAM as a monotherapy for MDD. We only included TEAM that could be used in context of clinical setting in Korean Medicine. Outcomes were the Hamilton Depression Rating Scale (HAMD) and total effective rate (TER). After comprehensive electronic search of 11 databases, we included 28 randomized controlled trials (RCTs) that compared HM as monotherapy with antidepressant for MDD. Meta-analysis showed that TEAM had significant benefits in reducing HAMD (MD=-0.40, 95% CI: -0.67 to -0.13, p=0.003, I2=85%) and improving TER (RR=1.06, 95% CI: 1.02 to 1.10, p=0.003, I2=0%). It also appeared to be safer than antidepressant in terms of adverse effects. Methods used for RCTs were poor and the quality of evidence was graded ‘low’ or ‘moderate’. These findings indicate that the use of HM as a monotherapy might have potential benefits in MDD treatment as an alternative to antidepressant. However, considering the methodological quality of included RCTs, the clinical evidence is uncertain. Further well-designed RCTs are required to confirm these findings.