The aim of this study was to investigate biomimetic activity of water-soluble manganese porphyrin complexes with a series of meso-substituents of the porphyrin macrocycle in the electrocatalytic reduction of hydrogen peroxide in aqueous solutions and to obtain information on possible intermediates, processes, and mechanisms. Mn porphyrins were compared in the process of the electrocatalytic reduction of hydrogen peroxide at pH 4, 7.4, and 10 in the deoxygenated solutions and in the presence of oxygen. The highest sensitivity, defined as the reduction current increase in relation to the concentration of hydrogen peroxide, was found in the case of Mn(III) meso-tetra(N-methyl-4-pyridyl) porphyrin, MnTMPyP, in alkaline 2.9·10−2 A M−1 and acidic 1.6·10−2 A M−1 solutions in the presence of oxygen. The reduction currents at pH 7.4, 10, and 4 in the presence of H2O2 were about 4, 7, and 12 times higher, respectively, in the solutions with the MnTMPyP complex than those at a GCE without a porphyrin complex in the solution. The electrocatalytic reduction of hydrogen peroxide occurs in parallel with an oxidative degradation of the porphyrin catalyst depending on the conditions of the experiment and was most significant in the presence of oxygen. The effect of the functional substituents at the meso-positions of a porphyrin ligand on the electrocatalytic activity of the water-soluble Mn(III) porphyrins complexes is discussed and reaction mechanisms are proposed.