Two small series of Pt(IV) complexes of the general formula cis,cis,trans-[PtA2Cl2L2] (A = 2 NH3, series 1, or cyclohexane-1R,2R-diamine, dach, series 2, L = aromatic carboxylate of different chain length, i.e. –OCO(CH2)nC6H5, n = 0 (a), 1 (b), and 2 (c)) were synthesized and fully characterized, including X-ray structure analysis of one of them. The antiproliferative activity of the complexes was evaluated against a panel of eight human cancer cell lines, proving to be at the nanomolar level for the platinum-sensitive A2780 and at the sub-micromolar level for the chemoresistant mesothelioma cell lines. In contrast with Pt(IV) complexes bearing aliphatic carboxylates, whose antiproliferative potency increases with the number of carbon atoms, a clear structure–activity relationship cannot be drawn in the bis(benzoato) series. The inclusion reaction with cyclodextrins (CDs), a widely accepted approach for drug formulation, was performed in order to obtain adducts able to bypass the limitations imposed by the low water solubility of bis(benzoato) complexes. Phase-solubility tests demonstrated that b-CD was able to efficiently solubilize only the very active prototype [Pt(NH3)2Cl2(C6H5COO)2] 1a. Two methods were used to prepare the host–guest inclusion systems (i.e., simple solubilization at room temperature of 1a in solution containing excess of b-CD or thermal reaction with subsequent isolation of a solid adduct) and the resulting adducts were tested for cytotoxicity against the cancer cell lines. The presence of b-CD in solution did not decrease the remarkable antitumor activity of 1a, whereas the solid-state inclusion system underwent extensive aggregation, proving to be detrimental for Pt accumulation in the cells and, therefore, overall cytotoxicity.