Diabetes, with its consequences of premature death, complications, and economic costs, is a precursor to a public health crisis that is expected to worsen over the next several decades. The improvement of diabetes outcomes, specifically glycemic control as measured by glycosylated hemoglobin concentration (HbA1c), can impact this critical situation. A quantitative study was conducted that examined health literacy and patient trust as predictors of glycemic control. The related factors of demographics, socioeconomic status, diabetes knowledge, self-care activities, and depression were also considered. Implementing a cross-sectional, predictive design, a convenience sample of 102 patients with diabetes was recruited from two urban primary care clinics in the USA. A simultaneous multiple regression was conducted. The regression analysis was significant, with patient trust and depression accounting for 28.5% of the variance in HbA1c. There was a significant positive relationship between socioeconomic status and health literacy and between diabetes knowledge and health literacy. The results support promotion of the patient-provider relationship, depression screening among individuals with diabetes, and exploration of new strategies for diabetes education. Future research is needed to advance the framework, ascertain which factors engender patient trust, and determine the role of health literacy in glycemic control.