Objective <p>To develop and optimize a baicalin-loaded soluplus-based hydrogel patch for enhanced wound healing applications.</p> Methods <p>Baicalin-loaded hydrogel patches were formulated using freeze–thaw method and optimized through 3 × 2 factorial design with varying concentrations of PVA (1.0–2.0&#xa0;g) and Soluplus (0.33–0.66&#xa0;g). The patches were characterized for physicochemical properties, <i>ex vivo</i> permeation, stability, skin irritation potential, and wound healing efficacy in rat models.</p> Results <p>Solubility studies revealed poor aqueous solubility of baicalin (0.052&#xa0;mg/ml) while FTIR confirmed drug-excipient compatibility. The optimized formulation BF6 (PVA 2.0&#xa0;g, Soluplus 0.495&#xa0;g) demonstrated superior folding endurance (378 ± 16.52), drug content (90.23 ± 1.32%), and swelling index (168.42 ± 5.93%). <i>Ex vivo</i> permeation studies showed enhanced baicalin delivery (93.24 ± 3.94% at 12&#xa0;h) with a flux of 5.73 ± 0.28&#xa0;mg/cm²/h. Accelerated stability studies confirmed minimal degradation (2.86% drug content reduction) after 3&#xa0;months. The formulation exhibited zero Draize score in skin irritation tests and significantly accelerated wound healing (92.13 ± 4.82% contraction by day 9) compared to standard treatment (83.45 ± 4.65%) and control (68.27 ± 4.23%).</p> Conclusion <p>The optimized baicalin-loaded soluplus-based hydrogel patch offers a promising approach for chronic wound management with enhanced healing rates, excellent stability, and safety profile. This first-in-class baicalin-Soluplus combination addresses the challenges of baicalin's poor solubility through systematic factorial optimization. while providing controlled drug delivery and optimal wound microenvironment, presenting significant potential for clinical translation in advanced wound care therapy. Future mechanistic studies are warranted to elucidate molecular healing pathways.</p> Graphical Abstract <p></p>