Background: Diabetic foot ulcers (DFUs) are common problems in diabetes. One of the most important factors affecting the quality of diabetes care is knowledge and practice. The current study aimed at determining the knowledge and practice of patients with diabetes regarding the prevention and care of DFUs. Methods: The current analytical, cross sectional study was conducted in Guilan Province (north of Iran) on 375 patients registered in the medical records as type 2 diabetes mellitus. Demographic characteristics, knowledge, and practice of participants were recorded in a questionnaire during face-to-face interviews conducted by the researcher. Descriptive and inferential statistics were performed using SPSS version18. Results: The mean score of knowledge was 8.63 ± 2.5 out of 15, indicating that the majority of participants had a poor knowledge (84.8%). The mean practice score was 7.6 ± 2.5 out of 15, indicating that a half of them had poor performance (49.6%). There was a significant and direct correlation between knowledge and practice. Knowledge level, place of residence, marital status, and history of admission due to diabetic foot were predictors of practice score. Conclusions: According to the low level of knowledge and practice in patients with diabetes regarding the prevention and care of DFUs, and considering the significant relationship of some demographics of patients with knowledge and practice scores, a targeted educational program is needed to promote knowledge of patients with diabetes.