Prevalence of depression is high among individuals with type 2 diabetes (T2D). The objective of the current study was to identify the socio-demographic, psychosocial, cultural, and clinical risk factors that predispose to depression, and resources that protect from depression among low income Latinos with T2D. Participants (N = 211) were interviewed in their homes upon enrollment. Multivariate logistic regression was used to identify factors associated with depressive symptoms based on a score of ≥21 on the Center for Epidemiological Studies Depression scale. Lower household income, interference of diabetes with daily activities, and more T2D clinical symptoms were associated with depression risk in the multivariate analyses. At each level of food insecurity the risk of depression was lower the higher the level of social support (P < 0.05). Findings suggest that social support buffers against the negative influence of household food insecurity on depression risk. A comprehensive approach is necessary to address the mental health needs of low income Latinos with T2D.