BACKGROUND: Strategies for the control of scabies should be adapted to local settings. Traditional communities in French Guiana have non-Western conceptions of disease and health. OBJECTIVES: The objectives for this study were to explore knowledge, attitudes and practices to identify potential factors associated with the failure of scabies treatment in these communities. METHODS: Patients with a clinical diagnosis of scabies, seen at either the Cayenne Hospital or one of 13 health centres between 01 April 2021 and 31 August 2021, were included as participants, and were seen again after 6 weeks to check for persistence of lesions. Factors associated with treatment failure were looked for both at inclusion and at 6 weeks. Semi-structured interviews were conducted with a diversified subsample of participants. RESULTS: In total, 164 participants were included in the quantitative component, and 21 were interviewed for the qualitative component. Declaring that the second treatment dose had been taken was associated with therapeutic success. Western treatments were not always affordable. Better adherence was observed with topical treatments than with oral ivermectin, whereas permethrin monotherapy was associated with failure. Scabies-associated stigma was high among Amerindians and Haitians but absent in Ndjuka Maroons. Participants reported environmental disinfection as being very complex. CONCLUSIONS: The treatment of scabies in traditional Guianan communities may vary depending on local perceptions of galenic formulations, disease-associated stigma and differences in access to health care. These factors should be taken into account when devising strategies for the control of scabies aimed at traditional communities living in remote areas, and migrant populations.