Sb(III) complexes of 3-aminoquinoxaline-2-carbonitrile 1,4-dioxides were prepared in order to improve the anti-Trypanosoma cruzi activity of these ligands. The in vitro evaluations demonstrated that in general upon metal complexation the activity of the 3-aminoquinoxaline ligands increased. Except for one compound, with solubility problems, coordination to antimony resulted in 2- to 12-fold increase of the trypanosomicidal activity. In addition, these complexes were equally or more active against T. cruzi than other metallic complexes with the same ligands previously evaluated in the same conditions. Computational study was performed in order to explain the effect of these metals in the anti-T. cruzi activity of 3-aminoquinoxaline-2-carbonitrile 1,4-dioxide ligands.