Biomolecule-engineered metal-organic frameworks (Bio-MOFs) are designed by incorporating biomolecules into or onto MOFs through covalent and non-covalent interactions. These composite frameworks exhibit unique catalytic and biological activities, making them highly suitable for various biocatalytic applications. In this review, we highlight recent advances in the material design, bioengineering methods, structural and functional regulation techniques, and biocatalytic applications of Bio-MOFs. From a materials perspective, we explore their unique structures and multifunctional properties, including high surface area, tunable pore sizes, and excellent biocompatibility. We also discuss various bioengineering techniques such as biomineralization and post-synthetic modification that are employed for their synthesis. Furthermore, we examine the structural and functional regulations of Bio-MOFs, which enhance catalytic activity and stability through interactions with enzymes, peptides, and other biomolecules. Finally, we analyze their applications in diverse biocatalytic reactions, including biosensors/sensors, drug delivery, catalytic therapy, organic wastewater purification, and emerging bio-energy science. This review underscores the pivotal role of biomolecules in enhancing the biocatalytic functions of MOFs and aims to inspire the design and synthesis of novel Bio-MOFs for future bio-related applications.