Despite the serious persistence of infectious diseases, low-income, indigenous people in southern Mexico are increasingly burdened by noncommunicable diseases, type 2 diabetes in particular. Most studies on diabetes and indigenous peoples focus on the dietary transition they are experiencing, with an emphasis on the biological role of processed foods and soft drinks on the onset of this disease. Little, however, is known about the synergistic interaction of alcohol abuse, diabetes, and inequality. This article adopts a syndemic approach to investigate how alcohol abuse among women and men in a rural, indigenous community in southern Mexico contributes to exacerbating health outcomes. Based on a one-year qualitative ethnographic study, this article advocates the use of a syndemic approach into the study of noncommunicable diseases because it offers critical insights into political economy, individual and social suffering, and the biosocial nature of health and illness.