The design of cost-effective oxygen reduction reaction (ORR) catalysts in microbial fuel cells (MFCs) remains a challenge. Herein, a mesoporous silica (mSiO₂) assisted protection strategy is developed to synthesize highly dispersed CuCo nanoalloys embedded in nitrogen doped carbon Cu/Co-NC@mS catalyst using zeolitic imidazolate framework (ZIF) as carbon and nitrogen sources. The results revealed that the mSiO₂ protection holds the potential to inhabit CuCo nanoalloys from aggregation and thus promotes the formation of highly dispersed small CuCo nanoparticles. The obtained catalyst with pyrolysis temperature (T) of 800?°C (Cu/Co-NC@mS-800) achieves the best ORR performance among Cu/Co-NC@mS-T catalysts, yielding a maximum power density of 1000?mW?m^?2 when employed as air cathode MFCs. The significantly enhanced ORR performance of Cu/Co-NC@mS-800 could be attributed to following aspects: a) highly dispersed small CuCo nanoalloy particles, improved mesoporous surface area and volume owing to mSiO₂ protection; (b) the formation of concave regular dodecahedron mesoporous structure with thin graphtic carbon layer as support; (c) the synergetic effect between CuCo nanoalloys. This work provides a facile strategy for the preparation of highly dispersed bimetal nanoalloys with enhanced electrocatalytic performance for energy-related applications.