Copper(II) complexes of the Schiff base ligands 2-((5-nitrofuran-2-yl)methyleneamino) phenol (HL1) and 2-(4-nitrobenzylideneamino)phenol (HL2) were prepared and characterized using physicochemical and spectroscopic techniques. In these complexes the Schiff base ligands acted as a bidentate donor bound to Cu2+ through the oxygen and nitrogen atoms in the deprotonated form. The electron paramagnetic resonance spectra, carried out on [CuCl(L1)(phen)].0.5H2O and [CuCl(L2)(phen)].2H2O complexes, showed the presence of only mononuclear forms. The Cu2+ complexes and ligands were evaluated for their in vitro trypanocidal activity. The complex [CuCl(L1)(phen)].0.5H2O was more active than the free Schiff base and also presented a superior effect to benznidazole, the reference drug. The antiproliferative activity of the Schiff bases and Cu2+ complexes were evaluated for their effect on seven tumor cell lines and showed a cytostatic and in some cases a cytotoxic effect. These compounds also presented binding properties to deoxyribonucleic acid (DNA) and moderate ability to quench the intrinsic fluorescence of albumins.