The use of alcohol and drugs is a significant issue faced by First Nations communities in Canada, which is accentuated by high rates of mortality and morbidity resulting from opioid use. The frequency of opioid-related emergency room visits and the higher prevalence of illicit prescription drug use disorders in First Nations populations suggest challenges. Methadone maintenance therapy programs are consistently found to be the most effective treatment for opioid dependence; however, due to financial, geographic, and cultural factors, Aboriginal individuals are less likely to initiate methadone maintenance therapy. Cree Nations Treatment Haven is the first on-reserve methadone maintenance therapy program in Canada and the present study aimed to evaluate this program from clients’ perspectives. Results indicated that individuals in treatment with higher rated improvement showed greater engagement, life quality, psychological functioning, physical health, relationships with family and friends, and a more positive opinion of services and less motivation for treatment, psychological distress, problems with alcohol, criminality, employment and life difficulties, and overall risk. Individuals with a more positive opinion of services reported higher engagement and lower motivation. Finally, individuals in treatment reported a decrease in drug use, high-risk, and criminal behaviours, and improvements in housing, employment status, and family support, since admission to the program. Future evaluation would be beneficial to solidify the present findings and clarify the importance of culture in treatment effectiveness.