Oxidative stress is involved in several parasitic diseases such as Chagas. Agents able to selectively modulate biochemical processes involved in the disease represent promising multifunctional agents for the delay or abolishment of the progression of this pathology. In the current work, differently substituted 3-carboxamidocoumarins exerting both antioxidant and trypanocidal activities are described. Among the compounds synthesized, compound 3 (N-(4-hydroxyphenyl)coumarin-3-carboxamide) showed the most interesting antioxidant profile, presenting 53.2% superoxide radical scavenging and the highest ORAC-FL value (ORAC-FL=1.87) of the series. In the trypanocidal study, compounds 9 (N-(quinolin-6-yl) coumarin-3-carboxamide) and 10 (N-(quinolin-3-yl)coumarin-3-carboxamide) presented high activity in epimastigote stage and low activity in trypomastigote stage, as well as low cytotoxic effects. Additionally, these compounds decreased mitochondrial transmembrane potential in epimastigote Dm28c. Based on these results, compounds 9 and 10 proved to be good candidates for further studies. Interestingly, the current study revealed that small structural changes in this scaffold allow modulating both activities, suggesting that these molecules present the desirable properties for the development of promising classes of antichagasic compounds.