© 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. Aims Depression in diabetes mellitus (DM) is common and is associated with poor health outcomes. Peer support DM interventions include encouraging interactions that could improve depressive symptoms. We examined intervention effects for those with and without depressive symptoms in a peer support trial. Methods The 1-year ENCOURAGE trial included 424 persons with DM living in rural Alabama. Intervention participants worked with community volunteers who encouraged participants to engage in daily self-management; control arm participants received usual care. Outcomes included HbA1c, body mass index (BMI) and quality of life (QoL) with EuroQuol-5D (range 0.0-1.0). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ-8, range 0-24). Generalized Additive Models (GAM) examined control-intervention differences in changes in HbA1c, BMI, and QoL for those with PHQ-8 ≥ 5 and PHQ-8 < 5. Results Of the 424 participants enrolled at baseline, 355 completed follow-up and had data were that could be included into the study; they were aged 60.2 ± 12.1 years, 87% African American, 75% female, and 39% insulin-treated. In an overall GAM adjusting for imbalance across trial arms and time-related covariates, depressive symptoms improved for all, but after 15 months of follow-up intervention, participants experienced greater reduction in PHQ-8 score than control participants (p = 0.01). In stratified analyses, those with PHQ-8 ≥ 5 had unchanged HbA1c, lost weight (p = 0.03) and improved QoL (p = 0.04). Those with PHQ-8 < 5 also had unchanged HbA1c and lost weight, but did not improve QoL (p = 0.06). Conclusions Peer support improved depressive symptoms for all, but resulted in greater weight loss and gains in QoL for those with baseline depressive symptoms compared to those without.