Novel organoplatinum(II) complexes with 2-acetylthiophene thiosemicarbazone (ATTSC) were synthesized. The reaction of K2PtCl4with ATTSC in 1:1 and 1:2 metal to ligand ratios yielded1[Pt4(ATTSC-2H)4·4DMF] and2[Pt(ATTSC-H)(ATTSC)Cl·3CH3OH)]. The crystal structures of these platinum chelates have been solved by single-crystal X-ray diffraction structure determinations and revealed metalation of the thiophene ring at C2 through platinum atoms. Further characterization of1and2was performed using electronic, IR, UV/vis, and NMR spectroscopies and elemental analysis. The in vitro antitumor activity of the ligand as well as1and2was determined against two different human tumor cell lines (HT-29 and HuTu-80). These tests revealed that the platinum(II) complexes are more cytotoxic than their ligand. The tetranuclear complex1shows higher antiproliferative activity (IC50= 1.2 and 1.5 µM) when compared to2(IC50= 3 and 5.9 µM), while the ligand has IC50values of 8.6 and >10 µM. Compounds1and2can therefore be considered as agents with potential antitumor activity.