Mental health problems are prevalent among drug users. Methadone maintenance treatment (MMT) is an evidence-based effective treatment for drug addiction; however, there are few studies investigating depression, suicidal ideation, and their related factors among MMT users. In this cross-sectional study, 648 MMT users were recruited from six MMT clinics in Guangzhou, China. Data were collected through face-to-face interviews by trained interviewers. Of all participants, 270 (42.7%) exhibited probable depression (Depression Subscale of the Chinese short version of Depression, Anxiety, and Stress Scale (DASS-D), score ≥ 10) and 99 (15.3%) reported having suicidal ideation in the last six months. After adjusting for significant socio-demographic characteristics, all studied variables, including drug use history, social support, family support for MMT use, and satisfaction toward MMT services were significantly associated with both probable depression and suicidal ideation in the last six months. Furthermore, depression fully mediated the associations between drug use history, satisfaction toward MMT services, and suicidal ideation. In the final multivariate models, probable depression was associated with social support (OR = 0.88, 95% CI = 0.83–0.93) and satisfaction toward MMT services provided by doctors (OR = 0.59, 95% CI = 0.40–0.86), while for suicidal ideation, social support (OR = 0.85, 95% CI = 0.78–0.92) and probable depression (OR = 5.94, 95% CI = 3.39–10.42) were significant. The findings suggest that there are unmet mental health needs among MMT users. For countries with limited resources of psychological services, mental health care toward MMT users should be implanted into current health care settings and incorporate components such as social support, family’s understanding of MMT, and service satisfaction.