A biomimetic mineralization approach has been developed to house and protect natural enzymes with metal–organic frameworks (MOFs). In this study, a mesoporous MOF-based nanobiocatalyst was designed with an easy iron mineralization approach. Candida rugosa lipase (CRL) was chosen as the model enzyme. The nanobiocatalyst (Fe@CRL@ZIF-8) was characterized by Fourier-transform infrared, scanning electron microscopy and transmission electron microscopy (FTIR, SEM and TEM). The activity of the prepared nanobiocatalyst was tested by hydrolysis of p-nitrophenyl palmitate. It was observed that the enzyme loading values of Fe@CRL@ZIF-8 and CRL@ZIF-8 were 7.2 mg/g and 1.55 mg/g, and their activities were found to be 113.1 U/g and 30.36 U/g, respectively. Fe@CRL@ZIF-8 showed lipase activity 3.72 times higher than CRL@ZIF-8. The prepared nanobiocatalyst (Fe@CRL@ZIF-8) exhibited improved stability, and it retained 80% of its initial activity after 5 reuses. The easy, fast, and cost-effective process of iron mineralization opens up new possibilities for the use of biomacromolecules.