Background: Complex interacting social, economic and historical factors influence the availability and uptake of alcohol and drugs, including among Indigenous communities. Self-harm and suicide as well as homelessness and incarceration, can both precede and result from drug and alcohol use. Rates of self-harm, suicide and incarceration among Aboriginal and Torres Strait Islander people in Australia are among the highest in the world and drug and alcohol treatment programs need to address these underlying complexities. This study examines whether an 'holistic' residential drug and alcohol treatment program for adolescents, with over 30% of clients identifying as Aboriginal and Torres Strait Islander, can improve outcomes post-discharge, including reducing self-harm, suicide attempts, arrests and alcohol and drug use. The program addresses substance use, mental health, employment, accommodation, social/community and family life. Program admission and 3 months' post-discharge data from 2007 to 2016 were analysed. Results: From 2007 to 2016, 619 Aboriginal and Torres Strait Islander young people were admitted to the program; 247 stayed in the program for 30 days or more; 89 were successfully followed up three months post-discharge to determine whether there was a significant improvement from baseline using the McNemar's Test and the Wilcoxon Signed Ranks Test. On admission, 18 people (20%) of the study population reported attempting suicide in the last 3 months and 23 people (30%) reported self-harm. Most had been engaged in the criminal justice system, with 67 people (75%) having been to court and 62 people (70%) arrested one or more times in the past 3 months, with 35 people (41%) in unstable housing, reporting having lived in three or more places in the previous 6 months. At 3 months post-treatment, all (n = 18) who reported suicide attempts in the 3 months prior to admission reported no attempts in the prior 3 months at follow-up. There was also a significant reduction in self-harm with 23 young people out of the 27 who reported self-harm at baseline not reporting self-harm at follow up (85%) and in the proportion of adolescents who reported using cannabis, amphetamines and alcohol, as well as a reduction in the proportion who reported being arrested. Conclusions: The findings provide support for an 'holistic' residential treatment program as an approach to improve health and related outcomes for Aboriginal and Torres Strait Islander young people. In addition to a focus on multiple aspects of a young person's life in treatment, culturally relevant modes of treatment and support should be a future focus to further strengthen programs when Aboriginal and Torres Strait Islander young people are over-represented in the client group.