| Summary: | Background: <i>Hippeastrum</i> species have a wide range of biological properties. In Argentina, this genus comprises ten widely distributed species. Purpose: To evaluate the antiparasitic and anticholinesterase activities and chemical profiles of seven Argentinean <i>Hippeastrum</i> species and determine the synergism between the major isolated alkaloid—montanine—and benznidazole in anti-<i>Trypanosoma cruzi</i> activity. Methods: The antiparasitic activity was evaluated through antiproliferative and viability assays against <i>T. cruzi</i> epimastigotes. Synergism assays were performed using the Chou–Talalay method. AChE and BuChE inhibitory activities were also assessed. The alkaloid composition was obtained using GC-MS analysis. Results: All extracts showed strong growth inhibition of <i>T. cruzi</i> epimastigote proliferation. The extracts from <i>H. aglaiae</i>, <i>H. aulicum</i>, and <i>H. hybrid</i> stand out for their potent and total growth inhibition, which was comparable to benznidazole. The <i>H. reticulatum</i> extract showed strong Acetylcholinesterase (AChE) inhibitory activities, while five species showed moderate Butyrylcholinesterase (BuChE) inhibition. Fifteen alkaloids were identified by means of GC-MS. Regarding the synergism assessment, the highest synergistic effect was obtained from the combination of montanine and benznidazole. Conclusion: <i>Hippeastrum</i> species bulb extracts from Argentina were shown to be a good source of antiparasitic alkaloids and cholinesterase inhibitors. The synergism between montanine and benznidazole emerges as a potential combination for future studies to treat Chagas disease.
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