<p>Wound healing is a complex process that involves the interplay of infection, inflammation, and tissue regeneration. Nevertheless, the conventional therapies tend to treat these processes individually. Silver nanomaterials have been found to serve as platforms for surface chemistry and controlled ion-release kinetics, conferring a wide array of biological activities beyond their traditional antimicrobial applications and making them promising therapeutic platforms with broad-spectrum antimicrobial, immunomodulatory, and regenerative properties. Their versatile physicochemical properties, such as size and morphology. This review provides a critical, detailed examination of the biological processes that determine the therapeutic effects of silver nanomaterials, as well as their design principles and physicochemical properties. We discuss their multi-target antimicrobial effects against bacterial, fungal, and viral infections, as well as their role in regulating innate and adaptive immunity during wound healing, including in biofilm infections. These materials, along with soft-tissue and internal-organ repair, are discussed in both cutaneous and non-cutaneous applications, as well as in orthopedic and dental applications. Moreover, the most significant translational considerations, such as safety, dose-dependent toxicity, biodistribution, the long-term fate, and regulatory factors, are critically examined. The review highlights the importance of drawing on insights from materials science, microbiology, immunology, and regenerative medicine to demonstrate how rationally designed silver nanomaterials can address unmet clinical needs and identify opportunities for their safe and effective clinical use.</p> Graphical abstract <p></p>