Depression and antidepressant medications increase risk for type 2 diabetes. Cambodian-Americans have exceedingly high rates of both depression and diabetes. This paper reports outcomes of a diabetes prevention trial for Cambodian-Americans with depression. Primary outcomes were HbA1c, insulin resistance and depressive symptoms. Participants were aged 35–75, Khmer speaking, at risk for diabetes, and met study criteria for likely depression by either (a) antidepressant medication and/or (b) prolonged elevated depressive symptoms. Participants were randomized to one of three community health worker (CHW) interventions: (1) lifestyle intervention calledEat, Walk, Sleep(EWS), (2) EWS plus medication therapy management sessions with a pharmacist/CHW team to resolve drug therapy problems (EWS + MTM), or, (3) social services (SS; control). Assessments were at baseline, post-treatment (12 months), and follow-up (15 months). The n = 188 participants were 78% female, average age of 55 years, half had a household income < $20,000, and modal educational attainment was 7.0 years. Compared to the other arms, EWS + MTM showed a significant decrease in HbA1c and a trend for reduced inflammation and stress hormones. Depressive symptoms improved for EWS and EWS + MTM relative to SS. There was no change in insulin resistance. Cardiometabolic and mental health can be improved in tandem among immigrant and refugee groups.