In the present study, we sought to reveal how embedding oxidoreductase enzymes in a metal-organic framework influences restoring the biofunctionality when encapsulated within zeolitic imidazolate framework (ZIF-8 and ZIF-90), wherein these biocomposites were explored for their cellular metabolic activity using the (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) (MTT) assay on A549 lung cancer cells and NIH3T3 (mouse fibroblasts) cells. We chose two biocomposites, namely catalase-encapsulated ZIF-8 and ZIF-90, wherein the enzyme was encapsulated at varied loadings through a rapid self-triggered nucleation around the protein surfaces of the enzyme. Interestingly, this embedding pattern of catalase in both ZIF-8 and ZIF-90 depended on the surface chemistry of the enzyme. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy analysis revealed the stability of the encapsulated enzyme in the nanospace of the ZIF-8 and ZIF-90 frameworks. Investigation of the cellular metabolic activity by the MTT assay of Cat@ZIF-8 and Cat@ZIF-90 on the lung cancer cell A549 showed cell viability enhancement in the case of Cat@ZIF-8 at a higher percentage compared to that of Cat@ZIF-90. A similar metabolic activity assay was performed with the internalization of Cat@ZIF-90 for NIH3T3 (mouse fibroblasts) cells. The revealed difference between the MOF compounds was due to the nano-confinement effect in ZIF-8 compared to ZIF-90, which can accelerate the utilization in cellar metabolic activity.