Objective: Depression affects people living with HIV (PLWH) compliance leading to poor control infection. Previous observational studies showed an anti-depression effect of green tea extract (GTE). The therapeutic effect of GTE on depression were investigated in PLWH receiving antiretroviral therapy (ART). Methods: Fifty PLWH on ART with diagnose of mild to moderate of depression, participated in a double-blind, placebo-controlled trial and underwent 12 weeks of treatment with either 400 mg GTE capsules or placebo twice daily. The Hamilton depression scale of patients was measured before, 6 weeks and 12 weeks after treatment in two groups. The primary outcome measure was performed to evaluate the efficacy of GTE in improving depressive symptoms. Results: The mean of Hamilton score showed a significant difference between the two groups after 12 weeks (P = 0.035). Repeated measures ANOVA test showed a significant effect for time × treatment interaction on the Hamilton mean score between the two groups (P = 0.000). Conclusion: It seems the use of GTE capsules in PLWH on ART is safe and could lead to greater and more rapid improvement in depressive symptoms than placebo. Thus it can be considered as an alternative therapy for mild to moderate depression. Further studies with higher sample size and longer follow-up and comparisons with other antidepressive drugs are warranted.