Interactions of the Ni2+, Cu2+, and Zn2+ ions with the simplest dipeptide glycylglycine (GlyGly) are explored using various experimental and computational techniques. Solid and aqueous phase syntheses of the metalated GlyGly complexes (by solid-state grinding and by coprecipitation respectively) lead to the same products, as confirmed by physicochemical and spectral properties which indicate metal-coordination through the -NH2 and -CO2- groups of the dipeptide. Phase-diagram and kinetic studies of the solid-phase reaction between GlyGly and copper acetate suggest that complexation occurs in 1:2 (metal/ligand) stoichiometry via a facile kinetic pathway (a barrier of only 22.22 kJ/mol). The right-handed a-helical conformer of GlyGly is considered in DFT modeling studies in gas and aqueous phases elucidating the effects of metalation and solvation upon structural, electronic, and vibrational properties of the complexes. The complexes are found to follow the stability order Cu2+ > Ni2+ > Zn2+ corroborating the Irving-Williams series. The Ni(GlyGly)(2) complex is predicted to exist in its low-spin state. Hydration effects on structural aspects of the complexes are also investigated computationally. The BHandHLYP/6-311++G(d,p) level describes the Cu(GlyGly)(2) complex more efficiently than the B3LYP/6-311++G(d,p) level (which, however, better predicts the vibrational spectra of the systems). Absorption titration experiments with calf thymus DNA together with in silico docking and molecular mechanical studies reveal that these metaldipeptide complexes are DNA minor-groove binders primarily through H-bonding interactions, yielding a DNA-binding affinity order of Ni2+ > Zn2+ > Cu2+.