Current chemotherapy for leishmaniasis faces significant limitations due to high toxicity, prolonged treatment regimens, and increasing parasite resistance, highlighting the urgent need for innovative treatment strategies. This study aimed to evaluate the in vitro activity of 1,2,3-triazole derivatives against promastigotes and amastigotes of Leishmania amazonensis, as well as their cytotoxicity in murine macrophages. Additionally, we investigated the mechanism of parasite death through different biochemical and cellular indicators of cell death parameters. Our results underscored the importance of the salt form, as the neutral form showed no inhibition of parasite growth. In contrast, the triazole-derived salt demonstrated promising selective index (SI = 34.28) and antileishmanial activity (IC