Background: Diabetes Mellitus (DM) is a major public health problem worldwide and Nepal is not an exception. Complications of DM are in rise which results in major disabilities and poor quality of life. But evidences show that adoption of self-care practices can prevent those complications leading a healthy and quality life. Self-care practice is closely related to self-efficacy. Thus, present study aimed to assess perceived self-efficacy and self-care practices and to examine relationship between perceived self-efficacy and self-care practice of patients with Diabetes. Methods: This analytical cross-sectional study conducted in Patan Hospital among 100 patients was reviewed and approved by Institutional Review Committee. Samples were selected purposively and data was collected by face to face interview technique. Diabetes Self-Efficacy Scale and self-care practice questionnaire was used to measure self-efficacy and self-care practice, respectively. Results: Fifty nine percent and 81% of participants had moderate level of perceived self-efficacy and good self-care practice, respectively. There was significant moderate positive (r=0.62, p<0.001) correlation between perceived self-efficacy and self-care practice even after controlling the variables (e.g. age, gender and participation in educational program regarding self-care). Conclusion: The self-efficacy of participants was moderate and self-care practice was good. However, self-care practice was very low on foot care and exercise. The significant positive relationship between perceived self-efficacy and self-care practice highlights the need for conducting educational activities for patients with DM to increase self-efficacy thereby increasing self-care practice.