The reactions between glycine and ammonia and the dimerization of glycine with and without Mg²⁺, Ni²⁺, Cu²⁺ and Zn²⁺ cations as catalysts have been studied as model reactions for peptide bond formation using the Becke3LYP functional with 6-311 + G(d,p) and 6-31 + G(d) basis sets. The B3LYP method was also used to characterize the 12 gas-phase complexes of neutral glycine, its amide and glycylglycine with Lewis acids Mg²⁺, Ni²⁺, Cu²⁺ and Zn²⁺, respectively. Enthalpies and Gibbs energies for each reaction have been calculated to determine the thermodynamics of the reactions investigated. A substantial decrease in the reaction enthalpies and Gibbs energies was found for glycine–ammonia and glycine–glycine reactions catalyzed by Mg²⁺, Ni²⁺, Cu²⁺ and Zn²⁺ ions compared with those of the uncatalyzed amide bond formation. The formation of a dipeptide is a more exothermic process than the creation of simple amide from glycine. The catalytic effect of the transition metal ions Ni²⁺ Cu²⁺ and Zn²⁺ is of similar strength and more pronounced than that of the Mg²⁺ cation. The basicity order of the bases investigated is: NH₂CH₂CO₂H<NH₂CH₂CONH₂<NH₂CH₂CONHCH₂CO₂H. Interaction enthalpies and Gibbs energies of metal ion–base complexes increase as Mg²⁺<Zn²⁺<Cu²⁺<Ni²⁺.