Objective: To provide an estimate of the effect of interventions on comorbid depressive disorder (MDD) or subthreshold depression in type 1 and type 2 diabetes. Methods: Systematic review and meta-analysis. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomized controlled trials evaluating the outcome of depression treatments in diabetes and comorbid MDD or subthreshold symptoms published before August 2019 compared to care as usual (CAU), placebo, waiting list (WL), or active comparator treatment as in a comparative effectiveness trial (CET). Primary outcomes were depressive symptom severity and glycemic control. Cohen's d is reported. Results: Forty-three randomized controlled trials (RCTs) were selected, and 32 RCTs comprising 3,543 patients were included in the meta-analysis. Our meta-analysis showed that, compared to CAU, placebo or WL, all interventions showed a significant effect on combined outcome 0,485 (95% CI 0.360; 0.609). All interventions showed a significant effect on depression. Pharmacological treatment, group therapy, psychotherapy, and collaborative care had a significant effect on glycemic control. High baseline depression score was associated with a greater reduction in HbA1c and depressive outcome. High baseline HbA1c was associated with a greater reduction in HbA1c. Conclusion: All treatments are effective for comorbid depression in type 1 diabetes and type 2 diabetes. Over the last decade, new interventions with large effect sizes have been introduced, such as group-based therapy, online treatment, and exercise. Although all interventions were effective for depression, not all treatments were effective for glycemic control. Effective interventions in comorbid depressive disorder may not be as effective in comorbid subthreshold depression. Baseline depression and HbA1c scores modify the treatment effect. Based on the findings, we provide guidance for treatment depending on patient profile and desired outcome, and discuss possible avenues for further research.