The reactions of platinum(II) complexes, [PtCl 2 (dach)] (dach = (1R,2R)-1,2diaminocyclohexane) and [PtCl 2 (en)] (en = ethylenediamine) with biologically relevant ligands such as 5 -GMP (guanosine-5 -monophosphate) and L-His (L-histidine) were studied by UVvis spectrophotometry, 1 H NMR spectroscopy, and high-performance liquid chromatography (HPLC). Spectrophotometrically, these reactions were investigated under pseudo-first-order conditions at 310 K in 25 mM Hepes buffer (pH 7.2) and 10 mM NaCl to prevent the hydrolysis of the complexes. The [PtCl 2 (en)] complex reacts faster than [PtCl 2 (dach)] in the reaction with studied nucleophiles. This confirms the fact that the reactivity of studied Pt(II) complexes depends on the structure of the inert bidentate ligand. Also, the substitution reactions with L-His are always faster than the reactions with nucleotide 5 -GMP. The reactions of [PtCl 2 (dach)] and [PtCl 2 (en)] complexes with L-histidine are studied by 1 H NMR spectroscopy. The obtained rate constants are in agreement with those obtained by UV-vis. The same reactions were studied by HPLC comparing the obtained chromatograms during the reaction. The changes in intensity of signals of the free and coordinated ligand show that after a few days there is only one dominant product in the system.