Background: Mexico's health profile has changed significantly in the last decades as chronic diseases continue to increase. Type 2 diabetes mellitus (T2DM) prevalence in Mexico is among the highest in the world and now the leading cause of death in the nation. Oaxaca is one of the most impoverished, rural states in Mexico with the largest concentration of indigenous people in the country. Despite the increase in T2DM prevalence and associated risk factors in recent years in this area, little is known about this population's beliefs, understandings and practices regarding T2DM. In order to address this trend in T2DM growth, more research is needed regarding the existing cultural beliefs and behaviors related to T2DM in Oaxaca, which are key to informing diabetes prevention and control. Thus, this study, guided by an explanatory model (EM) for T2DM, explored the cultural beliefs of T2DM casualty, cures, and traditional medicine use among a sample of diabetics and non-diabetics in Oaxaca. Methods: The purpose of this cross-sectional study was to explore diabetes cultural beliefs and traditional medicine practices among a convenient sample of 158 diabetics and non-diabetics in central Oaxaca, Mexico. In-person Spanish-language survey data were collected to explore whether non-diabetics were more likely to endorse diabetes cultural beliefs than diabetics and to explore predictors of traditional medicine usage. The Spanish-language survey instrument assessed: socio-demographic and health related characteristics, traditional medicine use and cultural beliefs about diabetes. Results: Findings showed that diabetics and non-diabetics did not differ in their endorsement of traditional cultural bound beliefs. Results also showed that a younger age (OR=1.04) and endorsement of punitive/mystical retribution beliefs (OR=5.42) regarding diabetes etiology, predicted a greater likelihood of traditional medicine use. Discussion: These results may aid the efforts of health professionals in Oaxaca by providing culturally contextualized insights that may be drawn upon when developing relevant health curriculums and promotion methods specific to this population. These findings may also be beneficial in the development of programs for T2DM prevention, treatment and control among diabetics and non-diabetics in the region. Family and community collective cultural views of illnesses may be highly influential in forming corresponding diabetes illness and cure beliefs among diabetics and non-diabetics, particularly among younger individuals. Because of the important role that these social networks play in an individual's health beliefs and behaviors, a greater integration of non-diabetics and their cultural explanatory model for diabetes would provide a more comprehensive approach to diabetes prevention and management efforts. Further research is needed to understand the impact of diabetes cultural beliefs and health behaviors among diabetics, as well as culturally relevant prevention strategies in Mexico.