The objective of this study was to examine the association between biomedical markers of disease management and psychosocial constructs, while also assessing the correlates and predictors of variability for satisfaction with life (SWL) among African American and Hispanic participants with type 2 diabetes. Data were collected from 142 participants during their first visit within a collaborative care program. Pearson product moment correlations, a multiple linear regression, and a one-way analysis of variance were used to examine the research questions. Researchers found psychological distress, social support, and spirituality accounted for twice the amount of variance in SWL for African American participants compared to Hispanic participants. Social support was the strongest predictor of SWL for African American participants, while psychological distress was the strongest predictor of SWL for Hispanic participants. Social support moderated the relationship between psychological distress and SWL for Hispanic participants, but not African American participants. Spirituality did not moderate the relationship for either ethnic group. One significant relationship was noted for BMI and somatization; otherwise, no significant relationships were documented between psychosocial-spiritual and biomedical constructs, which may relate to limited variability in HbA1c. Clinicians and researchers who work with underserved minority patients with uncontrolled diabetes may see improvement in patients' SWL when screening, treating, and/or studying psychological distress, interpersonal strain, and existential struggles. It is important for practitioners and researchers to consider ethnic group differences in their work since some dissimilarity existed.