The biosafe plant extract, rich in bioactive compounds with anti-inflammatory and antioxidant properties, significantly contributes to wound healing by promoting tissue repair and regeneration. However, the powdered forms of these extracts face several limitations including poor water solubility, limited release in vitro, and compromised waterproofing and breathability. This study successfully developed a smart and bioactive wound dressing through co-electrospinning hydrophobic polylactic acid-H. rhamnoides L. petroleum ether extract with hydrophilic polyvinyl alcohol-Ag (PLAPEE/PVAAg). This innovative dressing exhibits robust properties such as anti-inflammatory and antibacterial activities primarily derived from bioactive compounds in PEE and Ag nanoparticles decorated within PVA nanofibers respectively. Additionally, the dressing's intelligent waterproofing, breathability, and interstitial fluid absorption create a moist environment that accelerates wound healing. Metabolomics analysis highlights the significance of glycolysis, the TCA cycle, arginine metabolism, linoleic acid/arachidonic acid metabolism, and glutaminolysis in wound healing. These enriched pathways not only stimulate extracellular matrix synthesis specifically collagen but also demonstrate anti-inflammatory properties while promoting angiogenesis thereby enhancing the wound healing process. As an innovative medical dressing, this smart bioactive solution holds immense potential for accelerating wound healing and tissue regeneration while paving a promising path for future advancements in personalized therapeutic strategies for enhanced wound care management.