Major Depressive Disorder (MDD) is substantially higher in people seeking Methadone Maintenance Therapy (MMT) as compared to the normal population. Erectile Dysfunction (ED) is one of the side effects of Methadone Maintenance Therapy (MMT) which is rarely explored as it is regarded as a sensitive topic. This study aims to determine the prevalence of MDD and its association with ED among MMT clients. A cross-sectional study was conducted involving 160 subjects who attended the Methadone outpatient clinic. The clients were given Patient Health Questionnaire-9 to screen for depressive symptoms and MINI International Neuropsychiatric Interview to diagnose MDD. ED was diagnosed using the 5-item International Index of Erectile Function. The results showed the prevalence of depression in clients on MMT was 30.6% and the prevalence of ED was 72.5%. On multivariate analyses, there were significant associations between ED with depression (P<0.05). Smoking also was found to be contributed to depression. Sociodemographic factors, comorbid medical illnesses, and illicit substance use were found to have no associations with depression. Therefore, given the prevalence of MDD and ED in MMT clients was high, routine assessment of depressive symptoms and sexual function in clients on methadone should be done to minimize their negative impact on the clients