Given that the diabetes burden is rising rapidly in low- and middle-income countries, it is critical to understand perspectives of people living with diabetes in these settings. This qualitative study examines perceptions of causality and treatment among adults with type 2 diabetes in rural Indigenous communities of Guatemala. We conducted semi-structured interviews with 29 people living with type 2 diabetes from a population survey in two majority Indigenous Guatemalan towns. Data were coded inductively and themes were elucidated by consensus. Participants emphasized strong emotional experiences and stress as perceived causes of diabetes, as well as diet and heritability. All participants took biopharmaceutical treatments, but many also endorsed diet, exercise, herbal remedies, and naturopathic products as important remedies. Perspectives from people living with diabetes in two rural Indigenous towns in Guatemala differ from the biomedical model of disease and have implications for clinical practice and program development.