Homelessness is linked to various social determinants of health, including poverty, racism, and limited healthcare access, which are worsened by health issues. The street medicine movement aims to provide direct medical care and harm reduction services to unsheltered homeless individuals in accessible settings. A case study of Street Medicine St. Louis examines how trust influences the use of these services. Qualitative interviews with 19 participants revealed that trust is essential for effective care. Trust was fostered through consistent outreach, respectful interactions, and non-judgmental support, which positively affected participants’ perceptions of and willingness to use harm reduction resources like sterile syringes, fentanyl test strips, and naloxone. The study concludes that building trust through respectful and person-centered outreach is crucial for successful harm reduction initiatives. Street medicine programs should focus on relational approaches to improve the effectiveness of their services for unhoused populations.