This study aimed to develop a curcumin-loaded bilosomal hydrogel for topical wound healing, addressing the poor aqueous solubility and low oral bioavailability of curcumin. Bilosomes were fabricated using the thin film hydration technique with cholesterol, Span® 60, and sodium deoxycholate or sodium cholate. The optimal formulation, composed of cholesterol/Span® 60 (1:10 w/w) and 5 mg of sodium deoxycholate, exhibited a particle size of 246.25 ± 11.85 nm, zeta potential of −36.75 ± 0.14 mV, entrapment efficiency of 93.32% ± 0.40%, and 96.23% ± 0.02% drug release over three days. This formulation was loaded into an alginate dialdehyde/chitosan hydrogel cross-linked with calcium chloride. The loaded hydrogel showed high water uptake (729.50% ± 43.13%) and sustained drug release (≈100% over five days). In vivo studies on male Albino rats demonstrated complete wound closure after three weeks, with proper healing mechanisms. The curcumin-loaded bilosomal hydrogel was found to be a robust, efficient, and user-friendly dosage form for wound healing.This study aimed to develop a curcumin-loaded bilosomal hydrogel for topical wound healing, addressing the poor aqueous solubility and low oral bioavailability of curcumin. Bilosomes were fabricated using the thin film hydration technique with cholesterol, Span® 60, and sodium deoxycholate or sodium cholate. The optimal formulation, composed of cholesterol/Span® 60 (1:10 w/w) and 5 mg of sodium deoxycholate, exhibited a particle size of 246.25 ± 11.85 nm, zeta potential of −36.75 ± 0.14 mV, entrapment efficiency of 93.32% ± 0.40%, and 96.23% ± 0.02% drug release over three days. This formulation was loaded into an alginate dialdehyde/chitosan hydrogel cross-linked with calcium chloride. The loaded hydrogel showed high water uptake (729.50% ± 43.13%) and sustained drug release (≈100% over five days). In vivo studies on male Albino rats demonstrated complete wound closure after three weeks, with proper healing mechanisms. The curcumin-loaded bilosomal hydrogel was found to be a robust, efficient, and user-friendly dosage form for wound healing.