Abstract: Trypanosoma cruzi, the causative agent of Chagas\' disease, which is widely disseminated in Central and South America, represents an endemic neglected disease located in this geographic region. Therefore, there is an urgent need for the discovery of new, more effective, and safer drugs for human use. Natural products have played a major role in the chemotherapy of parasitic diseases. Based on the observed biological activities of two kind of natural compunds, coumarins and chalcones, we have synthesized coumarin-chalcone hybrids with the aim of evaluating their activity against Trypanosoma cruzi, and their antioxidant properties. All derivates have shown moderate trypanocidal activity in the epimastigote stage (clone Dm28c) being compound 3 the one with the highest activity. These preliminary findings encourage us to future structural optimization of this compound. In spite of the moderate trypanocidal activity of coumarin-chalcone hybrids, they have been proved to be very good antioxidants. Based on these results, we can conclude that compounds 3 and 4 are potential candidates for in vitro studies of their antioxidant activity.