Abstract: Introduction and Aims. Substance misuse and psychological comorbidities can be common and may impact negatively on treatment outcomes. However, without appropriate tools, detecting psychological symptoms for Indigenous people can be difficult. This study assessed the appropriateness of an eight-item screening tool (based on Strong Souls) for measuring any relationships between substance use and psychiatric symptoms for Indigenous Australians. Design and Methods. Indigenous Australians attending secondary or tertiary education institutions or substance use rehabilitation facilities in the Northern Territory (n = 407; mean age = 27.82) were assessed for depressive, anxiety and psychotic symptoms. The group represented 45 language groups from 95 urban and remote communities. English comprehension was measured on a scale from 0 (no understanding) to 10 (excellent understanding; M = 7.99, SD = 2.31). Ordinal regression analyses examined any associations between demographic and substance use factors and psychological symptoms. Results. Compared with non-users, current cannabis users were significantly more likely [odds ratios (ORs) = 2.2–4.4] to experience depressive or anxiety symptoms. Frequent cannabis users experienced more symptoms than occasional users. Prior-inhalant users were more likely to feel lonely (OR = 2.18) compared with non-inhalant users. Frequent alcohol users were less likely (OR = 0.44) to feel sad than non-users. These results are interpreted with respect to previous research and methodological limitations. Discussion and Conclusions. Symptoms of depression or anxiety may be common for individuals seeking treatment for substance misuse and with minor improvement, these eight-items may provide a useful screen for psychological symptoms in Indigenous Australians.