Background Diabetes mellitus is a major global threat to public health. Reducing the daily obstacles of coping with the disease for patients with diabetes may improve management. Purpose The aim of this study was to investigate daily obstacles to coping with Type 2 diabetes mellitus (T2DM) and related factors. Methods A descriptive and cross-sectional design was used. Data were collected from 186 patients with T2DM who were hospitalized in an endocrinology clinic in Turkey. The Hospital Anxiety and Depression Scale and the Diabetes Obstacles Questionnaire were used to collect data. Multiple linear regression analysis was performed to explore the predictors of obstacles to coping in patients with T2DM. Results The highest mean score was achieved on the obstacles to coping with diabetes (2.57 +/- 3.78) among the subscales of the Diabetes Obstacles Questionnaire. After regression analysis, level of treatment compliance was identified as the most significant predictor (beta = .289,p< .001). Anxiety, depression, smoking status, and highest level of education were also identified as significant predictors. Conclusions On the basis of these results, nurses should plan and implement interventions to improve treatment compliance and assist patients to overcome obstacles to disease management. Moreover, patient anxiety, depression, and lifestyle behaviors should be addressed.