Background: Trust is pivotal for a productive relationship between patients and healthcare providers and is positively correlated with multiple clinical and humanistic outcomes. However, the impact of trust in healthcare providers on different domains of health-related quality of life (HRQoL) among diabetic patients has not been studied in detail. Purpose: The aim of this study was to examine the association between the physical, mental or psychological, social, and environmental domains of HRQoL with the patients' trust in their primary care physicians while controlling for several sociodemographic and clinical factors. The study was conducted among a sample of diabetic patients. Patients and Methods: This study had a prospective questionnaire-based, multi-center, crosssectional design. The patients were recruited from three public hospitals in Saudi Arabia. Patients' experiences and trust in their primary care physicians were assessed using the Health Care Relationship Trust (HCR-Trust) scale. HRQoL was assessed using the Arabic version of the World Health Organization Quality of Life-BREF (WHOQOL-BREF). Multiple linear regression was conducted to assess the relationship between HCR-Trust and the WHOQOL-BREF physical, psychological, social, and environmental domains controlling for age, Charlson Comorbidity Index (CCI) score, health literacy, sex, education, annual income, nationality, and illness duration. Results: Three hundred and sixty-four patients participated in the study. The scores in all four domains of WHOQOL-BREF were positively associated with HCR-Trust scores of the diabetic patients. Additionally, the scores in the physical (β = −10.26; 95% CI: −13.77 to −6.74; P < 0.0001) and psychological (β = −3.91; 95% CI: −7.44 to −0.38; P < 0.0001) domains were negatively associated with female gender. Furthermore, the physical domain score was negatively associated with the duration of illness (β = −0.26; 95% CI: −0.506 to −0.02; P = 0.032). The environmental domain score was positively associated with annual income (β = 2.31; 95% CI: 1.05 to 3.56; P = 0.030). Other patient characteristics, such as age and education, were not associated with the scores of any of the WHOQOL-BREF domains. Conclusion: Patient trust in healthcare providers is positively associated with different domains of HRQoL. Therefore, building and maintaining trust with patients is important to achieve favorable treatment outcomes.