OBJECTIVE: To use quantitative and qualitative methods to characterize the work patients with type 2 diabetes mellitus (T2DM) enact and explore the interactions between illness, treatment, and life. PATIENTS AND METHODS: In this mixed-methods, descriptive study, adult patients with T2DM seen at the outpatient diabetes clinic at Mayo Clinic in Rochester, Minnesota, from February 1, 2016, through March 31, 2017, were invited to participate. The study had 3 phases. In phase 1, the Patient Experience with Treatment and Self-management (PETS) scale was used to quantify treatment burden. In phase 2, a convenience sample of patients used a smartphone application to describe, in real time, time spent completing diabetes self-management tasks and to upload descriptive digital photographs. In phase 3, these data were explored in qualitative interviews that were analyed by 2 investigators using deductive analysis. RESULTS: Of 162 participants recruited, 160 returned the survey (phase 1); of the 50 participants who used the smartphone application (phase 2), we interviewed 17 (phase 3). The areas in which patients reported highest treatment burden were difficulty with negotiating health services (eg, coordinating medical appointments), medical expenses, and mental/physical exhaustion with self-care. Participants reported that medical appointments required about 2.5 hours per day, and completing administrative tasks related to health care required about 45 minutes. Time spent on health behaviors varied widely-from 2 to 60 minutes in a given 3-hour period. Patients' experience of a task's burden did not always correlate with the time spent on that task. CONCLUSION: The most burdensome tasks to patients with T2DM included negotiating health care services, affording medications, and completing administrative tasks even though they were not the most time-consuming activities. To be minimally disruptive, diabetes care should minimize the delegation of administrative tasks to patients.