In this work, biologically active α-lipoic acid (ALA) and its isologous 1,2-diselenolane (SeA) and cyclopentyl (CpA) analogues were investigated for their differences in redox potentials, cytotoxicity and ROS production. In addition, the corresponding Pt(IV) complexes comprising ALA (1–4), SeA (5–8) and CpA (9–12) as axial ligands were synthesized. Those Pt(IV) complexes were characterized by NMR spectroscopy, ESI-mass spectrometry and elemental analysis. The cytotoxicity study showed that 1,2-diselenolane containing Pt(IV) (1, 3 and 4) complexes are more cytotoxic than the 1,2-dithiolane analogues (5, 7, and 8) throughout all tested cell lines, intriguingly, cyclopentyl containing species (9, 11 and 12) are the most effective, in some cases even more potent than the parent drug oxaliplatin. Three representative complexes 2, 6 and 10 were further assessed for their redox potentials, reduction with AsA, lipophilicity, cellular accumulation and ROS production. It turned out that the cytotoxicity profile is an overall result of good lipophilicity, high cellular accumulation, and (partially) enhanced ROS generation.