Introduction: Depression is a mental disorder that is increasingly common nowadays. It can emerge as morbidity in chronic diseases such as rheumatoid arthritis (RA). The leaf extract of Moringa oleifera (MO) has shown to be a complementary therapy in depression, besides its anti-inflammatory role. This study aimed to evaluate the effect of MO leaf extract on Depression in RA patients. Methods: This quasi-experimental study with a pretest-posttest control group design comprised 32 RA patients. The participants were divided into the control (n = 16) and intervention (n = 16) groups. The intervention group received two MO leaf extract-containing capsules b.i.d. for 28 days. The depression was evaluated by Beck Depression Inventory (BDI-II) and serum cortisol test. Statistical analyses used both paired and unpaired t-tests. Results: The posttest means comparison of BDI-II and serum cortisol showed a significant difference between groups (p = 0.031 and p = 0.015, respectively). The pretest-posttest difference within the control group did not show significant improvement in BDI-II and serum cortisol (p = 0.076 and p = 0.106). Meanwhile, significant BDI-II and serum cortisol improvement were found in the intervention group (p = 0.003 and p = 0.048, respectively). Conclusion: MO leaf extract reduces depression in RA patients based on BDI-II and serum cortisol assessment.