Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 2 2025 06 15 73 82 EN Mahdiyeh Safary 1 Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2 GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran Mobina Tajdari 1 Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2 GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran Amirreza Peyrovinasab 1 Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2 GI Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran Seyyed Mohammad Hassan Modarressi Research and Development Department, Hora Pharmed Company, Tehran Iran Sakineh Alijanpour Department of Biology, Faculty of Science, Gonbad Kavous University, Gonbad, Iran Mohammad Hossein Modarressi Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran Amir Rezazadeh Department of Clinical Pharmacy, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran 2025 05 17 2025 06 30 Hyaluronidase, a group of enzymes that catalyze the hydrolysis of hyaluronic acid, plays a pivotal role in modulating the extracellular matrix and enhancing tissue permeability. Hyaluronidase has gained widespread attention for its diverse biochemical properties and expanding therapeutic potential. This review provides a comprehensive overview of hyaluronidase, focusing on its biochemical characteristics, mechanisms of action, and regulatory pathways. We examine its utility in preclinical models, highlighting its role in drug delivery, tissue remodeling, and cancer research. Clinically, hyaluronidase has been employed in various domains including ophthalmology, dermatology, oncology, and as an adjuvant in subcutaneous and intramuscular drug administration. Additionally, its role in reversing complications of dermal filler injections has led to increased use in aesthetic medicine. Despite its broad application, challenges such as immunogenicity, variability in enzyme sources, and potential adverse effects warrant continued investigation. Through an integrated analysis of current evidence, this review aims to elucidate the multifaceted roles of hyaluronidase and explore its emerging applications in modern medicine. https://abi.tums.ac.ir/index.php/abi/article/view/112 https://abi.tums.ac.ir/index.php/abi/article/download/112/106 https://abi.tums.ac.ir/index.php/abi/article/download/112/107