Novel composite nanofibers incorporating curcumin-loaded flexible nano-liposomes (CLFN-liposomes) were developed for applications in tissue engineering, dressings, and drug delivery and release systems in this research. The preparation of CLFN-liposomes for curcumin encapsulation through the ethanol injection method was explored through a factorial experimental design. The optimal conditions for CLFN-liposomes/polycaprolactone composite nanofiber (CLFN-liposomes/PCL) were explored using the Taguchi method, emphasizing the addition of PCL, operational voltage, and flow rate. Uniformly distributed CLFN-liposomes with a smaller mean particle size of 53.9 ± 7.4 nm and higher encapsulation efficiency of 47.3 ± 3.4 % were synthesized for effective penetration. The smallest nanofiber diameter (186.3 ± 62.3 nm) with a smooth and uniform distribution was obtained after obtaining the optimum combinations of 17 wt% PCL, 4 wt% CLFN-liposomes/PCL, 25 kV, and 0.25 mL/h flow rate. The release of curcumin from CLFN-liposomes/PCL nanofibers followed the Higuchi model kinetics, with extended release for up to 48 h due to the dual-stage release from the nano-liposomes to the nanofibers. CLFN-liposomes/PCL dressings exhibited improved wettability (70.7° ± 4.3), water uptake (730 ± 44.2 %), biocompatibility (96 %), antimicrobial activity (41.8 ± 0.8 mm and 38.0 ± 1.1 mm inhibition zone of Staphylococcus aureus and Escherichia coli), and sustained release of curcumin, surpassing existing dressings in various aspects. This, novel composite nanofibers incorporating curcumin-loaded flexible nano-liposomes were developed, with promising wound dressing and broad application prospects. This study provides a novel idea for the release and delivery of active components through liposomes.