Purpose: The aim of the study was to investigate, in a nationwide study, if diabetes and especially metformin exposure during neoadjuvant chemo-radiotherapy improves the oncological outcomes in patients with rectal cancer. Methods and materials: Patients undergoing neoadjuvant chemo-radiotherapy and curative intended resection for rectal cancer in Denmark between January 1, 2003 and July 1, 2015 were identified. Diabetes was defined as medically treated diabetes. Only patients who were either active users of antidiabetic medication at the beginning of the radiotherapy or never-users were included. Active users were matched with never-users 1:2 by propensity score. Subgroup analyses concerning metformin treatment were performed. The primary outcome of the study was disease-free survival and the secondary outcomes were recurrence free survival and all-cause mortality. Results: A total of 9799 patients were undergoing rectal cancer surgery with curative intend in the period. Of those, 2379 received neoadjuvant treatment up to one year preceding surgery. In total 459 patients were included in the study 154 patients with diabetes and 305 not diagnosed with diabetes. In the diabetes group, 53 were in active treatment with metformin. No statistical difference between the diabetes group and the non-diabetes group was shown with respect to disease free survival (HR 0.96, 95%CI 0.73–1.26, p = 0.77), recurrence-free survival (HR = 1.11, 95% CI 0.78–1.58, p = 0.56) or all-cause mortality (HR = 0.94, 95% CI 0.69–1.28, p = 0.69). Metformin treatment did not influence any of the outcomes. Conclusion: Our study does not support that diabetes or metformin use are associated with response to neoadjuvant chemo-radiotherapy in terms of disease-free survival, recurrence-free survival or all-cause mortality.