Until 2014, the overseas departments had not been included in Santé publique France’s Health Barometers. In 2014, a Health Barometer for the overseas departments was conducted, covering all overseas departments except Mayotte—a department established in 2011, which required significant adjustments to the survey methodology. In 2018–2019, this was achieved with the Mayotte general population survey, which surveyed residents of Mayotte (4,817 people aged 15–69, 1,637 people aged 3–14, and 791 people under 3) on various health topics (obesity, nutrition, diabetes, high blood pressure, tobacco, alcohol, sexual health, healthcare utilization, and healthcare avoidance). Conducting a health assessment in Mayotte was essential to inform health policies by taking into account the epidemiological and sociodemographic contexts through a health survey tailored to this specific territory (a hospital under constant strain, low medical coverage, over 9,000 births annually, and targeted health issues). This document provides methodological details on the design of the survey. Since a telephone survey was not feasible, it was decided to conduct a face-to-face study at participants’ homes using a questionnaire, supplemented by anthropometric measurements and specimen collection (blood samples collected by nurses and self-collected vaginal or urine samples). Conducting a survey that combined questionnaires with visits by nurses required the establishment of a specific multi-partner framework: with the Santé publique France contractor (IPSOS) regarding the interviewers and with the Regional Union of Nursing Professionals of the Indian Ocean (URPS OI) regarding the involvement of private practice nurses.