Both interpersonal trauma (IPT) and substance use are linked to mental health problems, however their interplay is understudied. This study will investigate the relationship between IPT, substance use and mental health in a large population-based sample. Participants included 3756 individuals, mainly young university students using a snowball sampling method. History of IPT was collected retrospectively using the Traumatic Experiences Checklist. Substance use was examined using the World Health Organization's Alcohol, Smoking and Substance Involvement Screening Test. Mental health symptoms were assessed by the DSM-5 Level 1 Cross-Cutting Symptom Measure. Moderation analyses were performed investigating the relationship between IPT, substance use, and mental health symptoms. Participants exposed to IPT had a higher prevalence of substance use (cannabis, alcohol, tobacco) and had more severe mental health problems than people without IPT. Substance use was associated with a blunted increase of depression, anxiety, and anger in trauma victims. A history of abuse was more strongly linked to substance use than neglect. Moderation analyses further revealed that cannabis use increased psychotic symptoms and psychotic symptoms increased cannabis use in participants with high levels of IPT. Our findings indicate that substance use worsens psychotic symptoms in IPT victims whilst dampening other mental health symptoms.