This review offers a comprehensive examination of recent advancements in the field of bio-metal-organic frameworks (bio-MOFs), encompassing their synthesis methodologies, associated challenges, biocompatibility considerations, and an exploration of their diverse applications. A particular emphasis is placed on the incorporation of biomolecules such as saccharides, nucleobases, amino acids, peptides, proteins, and porphyrins as organic linkers, facilitating the construction of novel bio-MOFs endowed with augmented properties. Significant findings underscore the exceptional physicochemical attributes, biocompatibility, and functional versatility of bio-MOFs in drug delivery, bioimaging, biosensing, separation, catalysis, and environmental remediation. In summation, bio-MOFs represent a promising interdisciplinary domain that seamlessly merges elements of biology, medicine, and materials science. Through meticulous optimization of biocompatibility, morphology, and multifunctionality, bio-MOFs hold substantial promise for advancements in biomedical, therapeutic, diagnostic, and environmental technologies. Subsequent research efforts should include elucidating toxicity mechanisms, standardizing synthesis protocols, conducting thorough physicochemical characterizations, and evaluating clinical feasibility.