Although approximately 70% of American Indians/Alaska Natives (AI/ANs) reside in urban areas, our knowledge of risk and protective factors among AI/ANs seeking substance use treatment within urban areas is limited. We analyze substance and commercialized cigarette use, AI/AN cultural identity and involvement, physical health and cognitive functioning, and mental health symptoms among 63 AI/AN adults seeking substance use treatment within an urban area in California. Alcohol (37%), marijuana (27%), and methamphetamine (22%) were the most commonly reported substances. Sixty-two percent used commercialized tobacco use. The majority of AI/AN adults (78%) engaged in at least one traditional practice during the past month and endorsed high levels of spiritual connectedness. Those who engaged in traditional practices demonstrated significantly less depression (p = 0.007) and anxiety (p = 0.04). Medical and mental health issues were not prominent, although participants revealed high levels of cognitive impairment. Results highlight the importance of utilizing AI/AN traditional practices for AI/AN adults seeking substance use treatment within urban areas.