Novel organoplatinum(II) complexes with 2-acetylthiophene thiosemicarbazone (ATTSC) were synthesized. The reaction of K
2
PtCl
4
with ATTSC in 1:1 and 1:2 metal to ligand ratios yielded
1
[Pt
4
(ATTSC-2H)
4
·4DMF] and
2
[Pt(ATTSC-H)(ATTSC)Cl·3CH
3
OH)]. 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 of
1
and
2
was performed using electronic, IR, UV/vis, and NMR spectroscopies and elemental analysis. The in vitro antitumor activity of the ligand as well as
1
and
2
was 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 complex
1
shows higher antiproliferative activity (IC
50
= 1.2 and 1.5 µM) when compared to
2
(IC
50
= 3 and 5.9 µM), while the ligand has IC
50
values of 8.6 and 10 µM. Compounds
1
and
2
can therefore be considered as agents with potential antitumor activity.