The synthesis, spectroscopy, structures, and chemical reactivity of the organometallic complexes [(COD)Pt(CCR) 2 ] and [(COD)Pt(CCR)(R′)] (COD = 1,5-cyclooctadiene, R = Ph, (Me)Ph (2Me, 3Me, or 4Me), (NO 2 )Ph (2NO 2 , 3NO 2 , or 4NO 2 ), (4F)Ph, (4OMe)Ph, 2Py (2-pyridyl); R′ = Me (methyl), Neop (neopentyl = 2,2-dimethyl-1-methyl), NeoSi (neosilyl = trimethylsilylmethyl), Bz (benzyl)) has been explored. The crystal structures reveal square-planar surroundings of the Pt atoms with short Pt−C(alkynyl) bonds (<2 Å) and almost perpendicular orientation of the CC− aryl group to the Pt coordination plane. Nonattractive π−π stacking and C−H•••F intermolecular interactions were observed in the crystal structures. Multinuclear ( 1 H, 13 C , 195 Pt, and 19 F) NMR spectroscopy reveals structures in solution and Pt−ligand bond strength. The thermal stability in organic solvents, the electrochemical stability, and the reactivity of the complexes in organic or aquatic (water-containing) solution toward the physiologically relevant species glutathione, chloride, and protons was tested, revealing remarkable stability or inertness of the complexes. Cytotoxicity experiments in HT-29 colon carcinoma and MCF-7 breast adenocarcinoma cell lines revealed highly promising activities for selected platinum alkynyl COD complexes.