Introduction: The overall incidence of malaria is declining in French Guiana, although gold miners working at illegal sites appear to be particularly affected by the disease. The objectives of this study were to determine the prevalence of malaria in this population, associated behaviors, and the level of parasite resistance to artemisinin-based drugs. Materials and Methods: Recruitment took place at camps frequented by gold miners along the Maroni River. The following procedures were performed: a rapid diagnostic test for malaria, a questionnaire, a blood sample for PCR, and genotyping of the pfK13 gene for PCR-positive cases of Plasmodium falciparum. Results: From January to June 2015, 421 gold miners were enrolled, predominantly men (70.6%) and Brazilians (93.8%). The prevalence of Plasmodium carriage determined by PCR averaged 22.3% (95% CI: [18.3–26.3]), with 84% being asymptomatic. The identified species were mainly P. falciparum (47.9%), followed by P. vivax (37.2%), plus 10.6% co-infections. At the time of their last malaria episode, 52.4% of gold miners had self-medicated, mostly with artemisinin-based drugs (93.8%), with poor adherence (37.8%). Analysis of the pfK13 gene did not reveal any mutations associated with resistance to P. falciparum Discussion: The high prevalence of asymptomatic carriers of Plasmodium constitutes a significant reservoir for transmission in the region. The widespread use of artemisinin-based drugs combined with poor treatment adherence are risk factors for the emergence of resistance, necessitating rapid action.