Background: Diabetes is a highly prevalent metabolic disorder in the world. Complications of diabetes mellitus can have an extreme effect on the quality of life in terms of physical and mental health, as well as social and environmental well-being. Objectives: The current study aimed to measure the quality of life, its determinants, and self-care behaviors in patients with type 2 diabetes. Methods: A descriptive cross-sectional study was conducted in the diabetes clinic of Imam Reza hospital in Mashhad on 140 patients with type 2 diabetes from October to December 2019. The Summary of Diabetes Self-care Activities (SDSCA) questionnaire and the World Health Organization Quality of Life-Brief (WHOQOL-BREF-26 items) were used for data collection. Data analysis was carried out with the Mann-Whitney test and ANCOVA. Results: The mean age of study participants was 58.41 ± 8.91 years, and the majority of them (67.14%) were female. The overall self-care score was 43.32 ± 10.93 in males and 39.93 ± 9.94 in females. The mean scores of the dimensions of quality of life were 61.29 ± 15.66 for physical health, 60.62 ± 13.70 for mental health, 68.67 ± 11.63 for social health, and 61.54 ± 14.88 for environmental health. Among self-care behaviors, physical activity (P = 0.006) was a stronger predictor of quality of life. Demographic characteristics (except for the duration of disease, family history, and age) showed significant correlations with the overall aspects of quality of life. Conclusions: The quality of life of people with diabetes was correlated with some demographic variables. However, the duration of disease, family history, and age did not have any effect on the quality of life. We found that the self-care behavior of physical activity was a significant predictor of quality of life in adults with diabetes. Therefore, it is important to implement programs to improve self-care behaviors.