Illegal gold miners in French Guiana, a French oversea department in Amazonia, often carry malaria parasites (up to 46.8%). While the Guiana Shield Region aims at malaria elimination, the high prevalence of Plasmodium in this hard-to–reach population in conjunction with frequent incorrect use of artemisinin-based antimalarials threaten with the emergence of resistant parasites. Usual malaria control strategies cannot be implemented in this particular context because of geographical and regulatory issues in French Guiana. Therefore new strategies targeting this specific population in the forest are required. Numerous discussions among health institutions and scientific partners from French Guiana, Brazil and Suriname have led to an innovative project based on the distribution of kits for self-diagnosis and self-treatment of Plasmodium infections. The kit-distribution will be implemented at the “resting sites”, which are areas across the border regularly frequented by gold miners. The pilot phase led by the Center of Clinical investigation of French Guiana will start in April 2018. The first objective is to increase the use of appropriate and complete malaria treatment after a positive malaria diagnosis with a rapid test, which will be evaluated with a before-and-after cross-sectional studies. Monitoring indicators will be collected from health mediators at the time of kit distribution and during subsequent visits, and from illegal gold miners themselves, through a smartphone application. The project funding is multisource, including the Ministries of Health of the three countries, WHO/PAHO, and the European Union. Despite potential biases, this project may be the best available solution to a specific and important public health challenge in the Guiana Shield. If the use of self-diagnosis and self-treatment approach is effective, this strategy could be sustained by Health Institutions in the Region.