This article describes the preparation and characterization of a selected series of coumarin derivatives with the aim of evaluating their antioxidant properties and their activity against Trypanosoma cruzi, the parasite responsible for Chagas disease. All the derivatives demonstrated moderate trypanocidal activity in the epimastigote and trypomastigote stages (clone Dm28c), with Compound 3 presenting the highest trypanocidal activity of the entire series, displaying higher activity than nifurtimox, which was used as a reference compound. In addition to the trypanocidal activity, this compound proved to have a very interesting antioxidant profile, as well as no cytotoxicity. These preliminary findings encouraged the authors to study the future structural optimization of this scaffold.