Objective: To investigate the diabetes-related distress and quality of life among people with Type 2 diabetes mellitus(2DM). Methods: A cross-sectional study carried out at the Clinical Research Centre at the University of Campinas, Brazil, between September 2020 and April 2021. Patients answered data regarding demographic and clinical variables, the Brazilian version of the Diabetes Distress Scale and the Diabetes Quality of Life Measure by telephone contact. The data were managed using the RedCap System. For statistical analysis of the data, the Mann–Whitney and Kruskal–Wallis tests were applied for comparisons, and the chi-square test for associations. The correlations were evaluated using the Spearman correlation coefficient. Results: Of the 302 participants recruited, 50.33% showed high diabetes-related distress. Patients with higher scores in the diabetes-related distress have shorter schooling (p <0.05), HbA1c (p<0.05), worse Diabetes Quality of Life total score (p<0.0001), in the Quality of Life impact (p<0.0001), in the social/vocational worry (p<0.05) and in the diabetes worry (p<0.0001) subscales when compared to the group with the lowest diabetes-related distress. Conclusion: Patients with higher scores for diabetes-related stress have impacts on their QOL. For that reason, the early screening of at-risk individuals with this condition through coordinated and well-planned protocols could result in fewer repercussions in the patient’s quality of life. Furthermore, it could improve their experiences throughout the follow-up of the disease.