The challenge of American tegumentary leishmaniasis (ATL) continues in Brazil, presenting a persistent public health issue despite initiatives aimed at public outreach, vector control and health education. To gain a deeper understanding of this disease, a study was conducted in an endemic region located in the northern region of the state of Minas Gerais, Brazil. The study monitored 30 resident patients diagnosed with ATL, using serum samples from 6 healthy individuals as controls. The localized cutaneous form of the disease was found to be predominant, with lesions appearing on various parts of the body and the majority of the affected individuals being male. The study found significantly higher levels of IgG anti-α-Gal antibodies in ATL-infected patients compared to healthy individuals. Treatment of 19 patients with meglumine antimoniate resulted in limited improvement in symptoms for most. Nonetheless, the study found that 12 patients who completed treatment with epithelialization of the lesions showed a significant decrease in IgG anti-α-Gal antibodies, indicating potential applications of this antibody in the diagnosis and monitoring of the disease. The study also identified Leishmania species in 7 analysed patients, revealing 6 cases infected by Leishmania braziliensis and 1 by L. infantum, with a significant difference in the anti-α-Gal responses. The findings of the study emphasize the urgent need for the development of human vaccines and innovative treatment strategies adapted to the diversity of Leishmania species causing cutaneous leishmaniasis and individual patient responses to improve the clinical management of ATL in Brazil and similar endemic regions.