Patient–provider communication is modifiable and is linked to diabetes outcomes. The association of communication quality with medical mistrust is unknown. We examined these factors within the context of a low-literacy/numeracy-focused intervention to improve diabetes care, using baseline data from diverse patients enrolled in a randomized trial of a health communication intervention. Demographics, measures of health communication (Communication Assessment Tool [CAT], Interpersonal Processes of Care survey [IPC-18]), health literacy (Short Test of Functional Health Literacy in Adults), depression, medical mistrust, and glycemic control were ascertained. Adjusted proportional odds models were used to test the association of mistrust with patient-reported communication quality. The interaction effect of health literacy on mistrust and communication quality was also assessed. A total of 410 patients were analyzed. High levels of mistrust were observed. In multivariable modeling, patients with higher mistrust had lower adjusted odds of reporting a higher CAT score (adjusted odds ratio [AOR] = 0.67, 95% confidence interval [CI] [0.52, 0.86], p = .003) and higher scores on the Communication (AOR = 0.69, 95% CI [0.55, 0.88], p = .008), Decided Together (AOR = 0.74, 95% CI [0.59, 0.93], p = .02), and Interpersonal Style (AOR = 0.69, 95% CI [0.53, 0.90], p = .015) subscales of the IPC-18. We observed evidence of an interaction effect of health literacy for the association between mistrust and the Decided Together subscale of the IPC-18 such that patients with higher mistrust and lower literacy perceived worse communication relative to mistrustful patients with higher literacy. In conclusion, medical mistrust was associated with poorer communication with providers in this public health setting. Patients’ health literacy level may vary the effect of mistrust on interactional aspects of communication. Providers should consider the impact of mistrust on communication with vulnerable diabetes populations and focus efforts on mitigating its influence.