American Indian (AI) communities experience a disproportionate rate of Type 2 diabetes (T2D) and cumulative exposure to stress. Although this link is well researched among various populations, it has not been examined among AI communities. Path analysis was used to examine a multiple-mediator model to explain how caregiver stress influences self-reported mental and physical health among 100 AI participants with T2D. Caregiver stress was negatively associated with physical and mental health.