This report describes the synthesis, characterization and biological activity of a series of platinum(IV) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] (Pt56MeSS) with non-bioactive, lipophilic and bioactive axial ligands. In an attempt to explore the anticancer activity potential of the Pt(IV) derivatives, 2D and 3D cytotoxic screening and a preliminary in vivo study were performed. The average IC₅₀ values of the platinum(IV) derivatives ranged from 1.26 to 5.39 μM, compared with 1.24 μM for Pt56MeSS, suggesting that the axial ligands have a relatively minor effect on the potency of the compounds. Preliminary in vivo studies indicate that the platinum(IV) derivatives of Pt56MeSS are active in vivo and can reduce the tumor to a similar extent to cisplatin.