A family of mesoporous non-precious metal (NPM) catalysts for oxygen reduction reaction (ORR) in acidic media, including cobalt-nitrogen-doped carbon (C-N-Co) and iron-nitrogen-doped carbon (C-N-Fe), was prepared from vitamin B12 (VB12) and the polyaniline-Fe (PANI-Fe) complex, respectively. Silica nanoparticles, ordered mesoporous silica SBA-15, and montmorillonite were used as templates for achieving mesoporous structures. The most active mesoporous catalyst was fabricated from VB12 and silica nanoparticles and exhibited a remarkable ORR activity in acidic medium (half-wave potential of 0.79 V, only ~58 mV deviation from Pt/C), high selectivity (electron transfer number > 3.95), and excellent electrochemical stability (only 9 mV negative shift of half-wave potential after 10,000 potential cycles). The unprecedented performance of these NPM catalysts in ORR is attributed to their well-defined porous structures with a narrow mesopore size distribution, high Brunauer-Emmett-Teller surface area (up to 572 m2/g), and homogeneous distribution of abundant metal-Nx active sites.