The oxidation of Met residues in proteins is a complex process, where protein-specific structural and dynamical features play a relevant role in determining the reaction kinetics. Aiming to a full-side perspective, we report here a comprehensive characterization of Met oxidation kinetics by hydrogen peroxide in a leptin protein case study. To do that, we estimated the reaction-free energy profile of the Met oxidation via a QM/MM approach, while the kinetics of the formation of the reactive species were calculated using classical molecular dynamics (MD) simulations. Our data, validated against the available experimental data on the Met oxidation in this protein, indicated that the protein's local and global motion represent the primary discriminating factor among residues' oxidation rates. Moreover, assuming that the free energy profile is independent of the specific protein system, the different reactivities of Met residues within five proteins (hGCSF, IL-1ra, leptin, somatotropin, and RNase) were qualitatively analyzed in terms of well-known structural/dynamic features, which can affect the kinetics of the whole process. The comprehensive analysis of the reaction thermodynamics and kinetics fingerprint enabled the identification of additional descriptors, helpful in assessing the susceptibility of protein-bound Met residues to oxidation.