Canada is experiencing an ongoing overdose crisis, driven by a toxic unregulated drug supply. Integrated safer supply pilot programs offer pharmaceutical alternatives, coupled with comprehensive support services, to individuals using unregulated drug supply who are at high risk of overdose. We collected data from December 2020 to January 2023 on clients receiving safer opioid supply from five frontline service providers in Toronto, Canada, using interviewer-administered questionnaires. We assessed the incidence rate ratio of self-reported overdose comparing pre- and post-enrolment in the programs and examined changes in the prevalence of social and substance use outcomes post-enrolment. Forty-one participants were recruited, of whom 26 were followed up for a median of eight months (interquartile range, 5.0–11.7). The incidence rate ratio of overdose comparing post-enrolment to pre-enrolment was 0.20 (95% confidence interval, 0.09–0.43). Participants reported several positive social and substance use outcomes at follow-up, including a reduction in reliance on the unregulated supply and reduced criminal activity. Future implementation of integrated safer opioid supply pilot programs with larger sample sizes and rigorous epidemiological designs could help further illustrate the potential impacts of these programs in reducing overdose rates in Canada.