Background Adherence to treatment regimen is one of the behaviors related to diabetes, which has predicted successful control of the disease and reduced its intensity as well as negative consequences. This study aimed to determine the relationship between spiritual well-being and hope, and adherence to treatment regimen in patients with type II diabetes referred to diabetes clinics. Methods In this descriptive-correlational study, 227 diabetic patients referred to healthcare centers and diabetes clinics affiliated to Shiraz University of Medical Sciences were selected via cluster sampling (clinics) followed by convenience sampling (patients). The study data were collected using a demographic information form, spiritual well-being scale developed by Ellison and Paloutzian, Herth hope scale, and adherence to treatment regimen questionnaire. Then, the data were entered into the statistical software and were analyzed using descriptive and inferential statistics. Results The results indicated that most participants had moderate spiritual well-being, high hope, and low adherence to treatment regimen. Additionally, spiritual well-being was directly associated with hope and reversely related to adherence to treatment. A significant reverse correlation was also observed between hope and adherence to treatment. Conclusion Considering the fact that spiritual well-being and hope were reversely associated with adherence to treatment regimen, further studies should be done in this field. Also patients' image of God and their interpretations of being sick might not be appropriate and need correction.