Phenazinic ligands and Ru(II)-based complexes were synthesized from natural products lapachol and lawsone and evaluated against T. cruzi, the etiological agent of Chagas disease. These new ruthenium compounds could provide promising trypanocidal drugs. Besides synthesis and trypanocidal activity, this paper reports photophysical features and computational details of the compounds. The fluorescent trypanocidal substances are promising derivatives for further studies aiming to find molecules active against parasites associated with neglected diseases.