SummaryMucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases “PubMed” and “Lilacs” from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.