Since the last decade, metal–organic frameworks (MOFs) have received great attention from the materials scientist community owing to their excellent storage capacities, high surface area with tunable porous structures, functionalization-friendliness and biocompatible nature, which enable MOF-based materials to be suitable for biomedical applications. Zirconium-based MOFs (Zr-MOFs) are comparatively stable with low cytotoxicity and high drug-loading capacity. Therefore, Zr-MOFs and their composites have been thoroughly investigated for various bio-related applications such as drug delivery, anti-cancer activity, bio-sensing, and imaging. This review article demonstrates the recently developed synthetic routes for various surface-functionalized Zr-MOFs with their advantages and disadvantages. This review concisely summarizes some important Zr-based MOFs employed for biomedical applications such as drug delivery, immunoassay, antitumor activity, cytotoxicity activity, etc. Finally, a comparative analysis of the mode of action of the Zr-MOFs with varying organic linkers for biomedical applications is also provided to afford new directions for further research.