A novel series of platinum(II) complexes bearing aliphatic amines and ligands with DNA-targeting properties was synthesized to achieve more potent and selective metallodrugs. We developed six new platinum-based drugs, which contain methylamine, 1a-c, and isopropylamine, 2a-c, both in the trans position to a selected targeting ligand: naphthalimide. The activity of the complexes has been evaluated in order to confirm the improvements from our proposed approach, and the complexes demonstrate better cytotoxic activity on cancer cell lines when compared with the ligands and, importantly, with cisplatin. Further studies were performed to assess their subcellular localization and binding mode to DNA.