Aims. To examine one-year changes in oxidative damage and inflammation level in type 2 diabetic patients undergoing behavioral treatment for subsyndromal depression. Materials and Methods. A randomized controlled comparison of psychoeducation (A), physical exercise (B), and enhanced treatment as usual (C) was performed in 209 eligible subjects in a tertiary diabetes care setting. Depressive symptoms (primary outcome) and selected biomarkers of oxidative damage and inflammation (secondary outcomes) were assessed at baseline and six- and twelve-month follow-up. Results. Out of the 74, 67, and 68 patients randomised into groups A, B, and C, respectively, 201 completed the interventions, and 179 were analysed. Participants in all three groups equally improved in depressive symptoms from baseline to one-year follow-up (repeated measures ANOVA; F = 12.51, p < 0.0001, η (2) = 0.07). Urinary 8-oxo-deoxyguanosine (u-8-oxodG) decreased (F = 10.66, p < 0.0001, η (2) = 0.06), as did sialic acid and leukocytes (F = 84.57, η (2) = 0.32 and F = 12.61, η (2) = 0.07, resp.; p < 0.0001), while uric acid increased (F = 12.53, p < 0.0001, η (2) = 0.07) in all subjects during one year. Improvement of depressive symptoms at 6 months significantly predicted one-year reduction in u-8-oxodG (β = 0.15, p = 0.044). Conclusion. Simple behavioral interventions are capable not only of alleviating depressive symptoms, but also of reducing the intensity of damaging oxidative/inflammatory processes in type 2 diabetic patients with subsyndromal depression. This trial is registered with ISRCTN05673017.