By incorporating Cytochrome c (peroxidase, Cyt c) into a skeleton of its corresponding synthetic MOF analogue (peroxidase mimic, CuBDC), approximately 12-fold catalytic efficiency (kcat/KM) enhancement is observed compared to free Cyt c. Meanwhile, the shield endowed by CuBDC prevents encapsulated enzymes from deactivation by trypsin digestion, thermal treatment and long-term storage in vitro. This concept of combining enzymes and their MOF mimics with enhanced enzymatic activity and stability may provide new insights into the design of highly active, stable enzyme-MOF composite catalysts and holds promise for applications in biocatalysis, biosensing and drug delivery systems.