This review on bioactive Hydrogels (Bio-HyGs) synthesizes current advancements in their design and utilization, particularly emphasizing their roles in drug delivery and wound healing. Bio-HyGs, including gelatin methacrylate (GM), polyethylene glycol (PEG), and poly(vinyl alcohol) (PVA), are highlighted for their effectiveness in treating chronic wounds like diabetic and pressure ulcers, leveraging their moisture retention and tissue regeneration capabilities. These hydrogels are designed for the controlled release of bioactive compounds such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), thereby facilitating healing without the need for initial cell seeding. The review also covers hydrogels embedded with antimicrobial agents like silver nanoparticles and quaternized chitosan, which are crucial for managing infected wounds. Additionally, advancements in thermoresponsive hydrogels that respond to temperature changes and the application of self-assembling peptides and 3D printing are discussed for their contributions to mimicking biological tissues, which enhance both drug delivery and wound healing. The review aims to provide a comprehensive understanding of structural and functional modifications in Bio-HyGs, exploring their potential in transforming clinical outcomes in wound treatment and drug delivery systems. © 2025 Elsevier B.V., All rights reserved.