The study aims to examine the risk factors for increased colorectal cancer (CRC) markers in patients with type 2 diabetes mellitus (T2DM). The 229 patients retrospectively reviewed were categorized into two groups: CRC tumor marker-positive and -negative groups. Patients who tested positive for all three of the following CRC markers were included in the CRC tumor marker-positive group: serum carcinoembryonic antigen, carbohydrate antigen 19-9 and septin9 methylation. Univariate analysis revealed that most CRC marker-positive patients had higher age, a family history of CRC, history of smoking and alcohol intake, high body mass index (BMI; overweight), longer history of T2DM, worse diabetes control (with high glycated hemoglobin A1c [HbA1c]), lower level of serum vitamin D (VD), high-density lipoprotein cholesterol and higher level of total cholesterol and triglyceride (TG). Logistic regression analysis showed that BMI, VD, HbA1c and TG were independent predictors of CRC marker-positive status (OR, 95% confidence intervals and P values were 1.912 [1.346–2.716], <0.001; 0.773 [0.633–0.943], 0.011; 9.082 [3.52–23.433], <0.001; and 11.597 [3.267–41.164], <0.001, respectively). In this retrospective study, high BMI, HbA1c and TG as well as low level of VD were correlated with CRC tumor marker-positive status in T2DM patients. Patients with these risk factors may benefit from more frequent screening for CRC tumor markers.