Background <p>Homelessness results from, and exacerbates, various social determinants of health, including poverty, racism, and inadequate healthcare access, which are further compounded by physical and mental health challenges. The street medicine movement seeks to address these disparities by providing direct medical care and harm reduction services to unsheltered homeless in low-barrier settings. The development of trust is critical to providing this form of care. Few studies have sought to understand the factors influencing trust development in street medicine encounters.</p> Methods <p>This case study of Street Medicine St. Louis aims to explore the factors that influence trust and how trust development impacts unhoused individuals’ perceptions and utilization of services and education provided by Street Medicine St. Louis. Qualitative semi-structured interviews were conducted with 19 participants who receive harm reduction services from Street Medicine St. Louis. Participants were selected via purposive sampling from shelters, encampments, and street locations to ensure a diversity of experiences.</p> Results <p>Findings highlight that trust, built through consistent outreach, respectful interactions, and non-judgmental care, directly shaped participants' perceptions and utilization of harm reduction resources, including sterile syringes, fentanyl test strips, and naloxone. Trust facilitated greater receptivity to education and increased willingness to apply harm reduction practices.</p> Conclusion <p>Building trust through consistent, respectful, and person-centered outreach is essential for effective harm reduction interventions. Street medicine programs should prioritize relational approaches to enhance uptake and impact of harm reduction services among unhoused populations.</p>