Novel platinum(II) complexes of 4′-substituted terpyridine ligands were synthesized and characterized. Each complex had a different biomolecule (amine, glucose, biotin and hyaluronic acid) as a targeting motif, potentially improving therapeutic outcomes. We demonstrated that complexes can self-assemble in water into about 150 nm nanoparticles. Moreover, the complexes were assayed in vitro toward a panel of human cancer cell lines (ovarian adenocarcinoma A2780, lung cancer A549, breast adenocarcinoma MDA-MB-231, neuroblastoma SHSY5Y) to explore the impact of the pendant moiety on the terpyridine toxicity. The platinum complex of terpyridine amine derivative, [Pt(TpyNH2)Cl]Cl, showed the best antiproliferative effect, which was higher than cisplatin and [Pt(Tpy)Cl]Cl. Selective in vitro antiproliferative activity was achieved in A549 cancer cells with the Pt–HAtpy complex. These findings underline the potential of these novel platinum(II) complexes in cancer therapy and highlight the importance of tailored molecular design for achieving enhanced therapeutic effects.