Over the past two decades, metal-organic frameworks (MOFs) have garnered substantial scientific interest across diverse fields, spanning gas storage, catalysis, biotechnology, and more. Zirconium, abundant in nature and biologically relevant, offers an appealing combination of high content and low toxicity. Consequently, Zr-based MOFs have emerged as promising materials with significant potential in biomedical applications. These MOFs serve as effective nanocarriers for controlled drug delivery, particularly for challenging antitumor and retroviral drugs in cancer and AIDS treatment. Additionally, they exhibit prowess in bio-imaging applications. Beyond drug delivery, Zr-MOFs are notable for their mechanical, thermal, and chemical stability, making them increasingly relevant in engineering. The rising demand for stable, non-toxic Zr-MOFs facilitating facile nanoparticle formation, especially in drug delivery and imaging, is noteworthy. This review focuses on biocompatible zirconium-based metal-organic frameworks (Zr-MOFs) for controlled delivery in treating diseases like cancer and AIDS. These MOFs play a key role in theranostic approaches, integrating diagnostics and therapy. Additionally, their utility in bio-imaging underscores their versatility in advancing medical applications.