Background: Diabetes, which is a non-communicable metabolic disease, imposes several complications and death worldwide. Strict lifestyle modification can prevent the progression of complications associated with diabetes. There is much evidence to show that following a healthy lifestyle such as healthy diet, moderate weight loss, and doing regular exercise can maintain normal blood glucose levels and minimize diabetes-related complications. Moreover, this lifestyle modification has a great impact on the control of hyperglycemia. Good knowledge, positive attitude, and good practice towards lifestyle modification can help to maintain a normal blood glucose level. Objective: The aim was to assess knowledge, attitude, and practice towards lifestyle modification of diabetes patients attending the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. Methods: An institutional-based crossectional study was conducted among diabetes patients attending chronic follow-up clinic from November 15, 2019 to December 15, 2019. Study participants were selected using a systematic random sampling technique. Data were collected by using a structured questionnaire and analyzed using the statistical package for social science version 20. Descriptive statistics were computed to determine the knowledge, attitude, and practice of diabetes patients toward lifestyle modification. Results: A total of 422 participants took part in this study with a response rate of 100%. In this study, 248 (59%) were knowledgeable, 223 (53%) had a positive attitude, and 172 (41%) had good practice, respectively. Conclusion: The findings of this study showed that the knowledge and attitude toward lifestyle modification were found to be good. However, the result of practice of lifestyle modification was low. Recommendation: Education about the disease condition and lifestyle modification (importance of physical exercise, weight loss, foot care, cessation of smoking, healthy dietary habit) to general society ought to be implemented by the responsible body.