In this paper, we present a comparative study of the catalytic properties of meso-tetrakis porphyrins modulated by the porphyrin metal center and meso ligands. Four porphyrin types were studied: the anionic Fe(III) and Mn(III) meso-tetrakis (4-sulfonatophenyl)porphyrin (TPPS4) and the cationic Fe(III) and Mn(III) meso-tetrakis (N-methyl-4-pyridyl)porphyrin (TMPyP). Fe(III)TPPS4 promotes predominantly homolytic cleavage of peroxides and exhibits catalytic efficiency tenfold higher than Mn(III)TPPS4, which cleaves peroxides predominantly by heterolytic scission of the O-O bond. The corresponding cationic Fe(III) and Mn(III) porphyrins exhibited the same catalytic efficiency that was significantly lower than the anionic pairs. The lower catalytic efficiency of Mn(III)TPPS4 relative to the corresponding iron porphyrin can be assigned to two factors: (1) the low reactivity of hydroperoxides as the oxygen donor to manganese(III) porphyrins and (2) the incapacity of oxomanganese to use peroxide as a reducing agent for recycling. Accordingly, the presence of 150 µM GSH duplicated the peroxide consumption by Mn(III)TPPS4. In cell conditions, the catalytic efficiency of Mn(III) should be increased due to the availability of axial ligands for the metal center and reducing agents such as glutathione (GSH) and proteins necessary for Compound II (oxomanganese IV) recycling to the resting Mn(III) catalyst. The use of thiol-reducing agents leads to GSH depletion, proteins’ oxidation, and consequently biological damages. In contrast to what was observed for Mn(III)TPPS4, GSH was efficient in the reduction of the resting Mn(III)TMPyP; it impaired peroxide consumption and free radical generation by the cationic porphyrin. Altogether, these results are in accordance with the antioxidant activity described for TMPyP.