Background: As a result of the intergenerational trauma impact and experience, Native Americans continue to exhibit trauma-related issues such as high rates of substance use. After leaving high school, the pressures and stress of continuing an education, finding work/employment, and the responsibilities related to family and tribal community obligations result in the Native American young adult being more vulnerable to substance use. Objective: The purpose of this paper is to report findings of the Talking Circle intervention impact on the outcome variables of Native-Reliance, substance use, stress, and behavioural health, depression, and cumulative trauma. Methods: Native-Reliance was the theoretical underpinning for the study, demonstrating culturally safe research. A pre-test/post-test one-group design was utilised to examine how the Talking Circle intervention influenced the outcome variables. In total, 75 Native American participants, ages 18–24, participated in the Talking Circle intervention sessions. Baseline pre-intervention measures were completed and were repeated at 6-month post-intervention. Results: At 6-month post-intervention, Native-Reliance significantly revealed an increase of 40.55 (t = 22.13, p < .001), sources of stress (SS) revealed a significant decline of 3.68 (t = −18.39, p < .001), behavioural health issues (BH) showed a significant decline of 3.63 (t = −15.36, p < .001), substance-related issues (SR) showed a significant decline of 3.57 (t = −15.24, p < .001), depression (PHQ-9) showed a significant decline of 4.85 (t = −17.02, p < .001), and cumulative trauma revealed a significant decline of 2.77 (t = −13.39, p < .001). Conclusions: The use of a culturally safe Talking Circle intervention evidenced a research approach that resulted in a positive impact on reducing substance use and increasing the well-being of young Native American young adults. Impact Statement: Culturally safer intervention environments are conducive to results in outcomes that are positive and effective.