Iron(V)-oxo complexes bearing negatively charged tetraamido macrocyclic ligands (TAMLs) have provided excellent opportunities to investigate the chemical properties and the mechanisms of oxidation reactions of mononuclear nonheme iron(V)-oxo intermediates. Herein, we report the differences in chemical properties and reactivities of two iron(V)-oxo TAML complexes differing by modification on the "Head" part of the TAML framework; one has a phenyl group at the "Head" part (1), whereas the other has four methyl groups replacing the phenyl ring (2). The reactivities of 1 and 2 in both C-H bond activation reactions, such as hydrogen atom transfer (HAT) of 1,4-cyclohexadiene, and oxygen atom transfer (OAT) reactions, such as the oxidation of thioanisole and its derivatives, were compared experimentally. Under identical reaction conditions, 1 showed much greater reactivity than 2, such as a 102-fold decrease in HAT and a 105-fold decrease in OAT by replacing the phenyl group (i.e., 1) with four methyl groups (i.e., 2). Then, density functional theory calculations were performed to rationalize the reactivity differences between 1 and 2. Computations reproduced the experimental findings well and revealed that the replacement of the phenyl group in 1 with four methyl groups in 2 not only increased the steric hindrance but also enlarged the energy gap between the electron-donating orbital and the electron-accepting orbital. These two factors, steric hindrance and the orbital energy gap, resulted in differences in the reduction potentials of 1 and 2 and their reactivities in oxidation reactions.