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Abstract Objective Diabetes distress typically causes depressive symptoms; common comorbidity of diabetes unpleasantly affects patients’ medical and psychological functions. Psychotherapeutic interventions are effective treatments to treat depressive symptoms and to improve the quality of life in many chronic diseases including diabetes. The present study investigated the efficacy of cognitive behavior therapy (CBT) to treat depressive symptoms in patients with type 2 diabetes mellitus (T2DM) using experimental and waitlist control conditions. Materials and Methods A total of 130 diagnosed patients with T2DM were taken from outdoor patients services of different hospitals in Faisalabad. Ninety patients met the eligibility criteria and were randomly assigned to experimental (n = 45) and waitlist control (n = 45) conditions. All the patients completed clinical interviews and assessment measures at pre-and post-assessment stages (16 weeks intervals). Medical consultants at the respective hospitals diagnosed the patients on the base of their medical reports and then referred those patients to us. Then we used different scales to assess primary and secondary outcomes: Diabetes Distress Scale (DDS) and Patient Health Questionnaire (PHQ) to assess primary outcomes, and a Short Health Anxiety Inventory (SHAI), a Revised Version of the Diabetes Quality of Life Questionnaire (DQLQ), and a General Medication Adherence Scale (GMAS) were used to investigate secondary outcomes. Repeated measure ANOVA was used to analyze the results. Results The findings indicated that patients who received CBT got a significant reduction in their diabetes distress F(1,60) = 222.710, P