A Native community developed the Wicozani Instrument, a 9-item self-report measure, to assess overall health and well-being from an Indigenous epistemology. The Wicozani Instrument measures mental, physical, and spiritual health and their importance to an individual's quality of life. The instrument's validity and reliability was examined through two studies. Study 1 utilized standardized measures from Native (i.e., Awareness of Connectedness Scale) and Western (i.e., Psychological Sense of School Membership and Suicide Ideation Questionnaire) epistemologies with Native and non-Native youth. Study 2 utilized a community created measure (i.e., Indigenous Healing Strategies Scale) with Dakota women. Results suggest the Wicozani Instrument is valid and reliable. The development of an Indigenous measure of overall health and well-being addresses Western atomistic frameworks, which often perpetuate the perception of Native identity as a risk factor for poor health, and works to disrupt the Cycle of Native Health Disparities.