BACKGROUND: In India, street vending remains an essential aspect of the informal economy as it serves as a source of employment and opportunities for livelihood to a substantial portion of the population. This study aimed to evaluate the physical health, mental health, and quality of life of the street vendors. MATERIALS AND METHODS: A cross-sectional study was conducted among the 422 individuals residing in the street vending job in the areas of Chennai, Chengalpattu, and Kanchipuram districts. The research study employed a purposive sampling method to carefully select a representative sample of street vendors. Physical Health Questionnaire (PHQ-14), the Depression Anxiety Stress Scale (DASS-21), and the World Health Organization Quality of Life (WHOQOL-Bref) was used to collect the data. Descriptive and inferential analysis was done using the statistical software IBM SPSS Statistics 24. RESULTS: Males are more prevalent in street vending compared to females. Over 98 of street vendors were against passing their jobs to their children. The most common medical disorders among street vendors were diabetes, hypertension, hyperthyroidism, and asthma. 51 had poor physical health, 22 experienced depression, 23 anxiety, and 39 stress. Age, marital status, educational status, place of residence, and occupation were identified as the primary risk factors associated with the health outcomes of this population. CONCLUSION: The primary factors contributing to individuals becoming street vendors include a lack of educational opportunities, reliance on family businesses, high unemployment rates, and economic hardship. Street vendors experienced significant physical health challenges, along with mild-to-moderate mental health problems, which ultimately impacted their overall quality of life. © 2025 Elsevier B.V., All rights reserved.