The strength of American Indian and Alaska Native (AI/AN) communities comes from generations of Indigenous traditions, language, culture, and knowledge. These strengths have been challenged by a complex set of systemic, structural, and social factors related to historical and intergenerational trauma that affects the health of AI/AN communities. Furthermore, AI/AN population health data often are inaccurate because of analytic coding practices that do not account for multiracial and ethnic AI/AN identification and inadequate because of statistical suppression. The 2023 national Youth Risk Behavior Survey included a supplemental sample of AI/AN high school students. Coding of race and ethnicity was inclusive of all AI/AN students, even if they also identified as another race or as Hispanic or Latino, providing comprehensive data on health behaviors and experiences among AI/AN high school students nationwide. Adult caretaker engagement and school connectedness and their association with 13 health behaviors and experiences were examined, including five types of current substance use, four indicators of emotional well-being and suicide risk, and four types of violence. Pairwise t-tests and adjusted prevalence ratios from logistic regression models identified significant associations between exposure and outcome variables. Among AI/AN students, having an adult who always tried to meet their basic needs, high parental monitoring, and high school connectedness were associated with lower prevalence of certain measures of substance use, poor emotional well-being and suicide risk, and violence. Compared with non-AI/AN students, the prevalence of current electronic vapor product use, current marijuana use, attempted suicide, and experience of sexual violence was higher among AI/AN students.This report presents the most comprehensive, up-to-date data on substance use, indicators of emotional well-being and suicide risk, and experiences with violence among AI/AN high school students nationwide. The findings suggest the importance of engaged household adults and school connectedness in promoting emotional well-being and preventing substance use, suicide-related behavior, and experiences of violence among AI/AN students. Understanding the historical context and incorporating Indigenous knowledge when developing interventions focused on AI/AN youths are critical to ensure such interventions are successful in improving AI/AN health and well-being.