Pt(IV) complexes are known as prodrugs that can potentially overcome cisplatin limitations by slowing down its reactivity and, once reduced, act as the corresponding Pt(II) drugs. We report a new approach toward trans Pt(IV) complexes, conceived to afford nonconventional active trans Pt(II) complexes with dual-targeting properties. The reduction of the complexes has been studied in the presence of ascorbic acid and glutathione, showing that different species are formed in the process. The interaction with DNA after reduction has been also studied and correlated to the formation of Pt(II) species. The cytotoxicity profile of the Pt(IV) complexes corroborated the rationale behind this approach.