Curcumin, a hydrophobic drug derived from the rhizome of Curcuma longa, exhibits significant bioactive properties, including antioxidant and antimicrobial potential. However, its poor water solubility and rapid degradation limit its practical applications. This study presents a novel design of electrospun nanofibers using curcumin/hydroxypropyl-β-cyclodextrin inclusion complex (HP-β-CD-IC) combined with pullulan to enhance thermal stability and controlled release. In uniaxial nanofibers, curcumin/HP-β-CD-IC is uniformly distributed, whereas in coaxial nanofibers, curcumin/HP-β-CD-IC serves as the core material, with pullulan as the wall material. X-ray diffraction and Fourier-transform infrared spectroscopy confirmed successful inclusion complex formation, with coaxial fibers showing no crystalline peaks of curcumin. Differential scanning calorimetry indicated enhanced thermal stability, with melting points shifting to 279.19 °C and 291.63 °C for uniaxial and coaxial fibers, respectively. Scanning electron microscopy and transmission electron microscopy verified the core-shell structure and uniform morphology. In vitro release studies revealed that coaxial fibers achieved higher cumulative release (93 ± 1.41 %) compared to uniaxial fibers (80 ± 2.82 %) over 350 min. Antibacterial tests demonstrated improved activity of coaxial fibers against S. aureus and E. coli. Addressing the critical need for stable and bioavailable delivery of hydrophobic bioactive compounds, this innovative coaxial nanofiber design holds great promise for revolutionizing applications in food technology and drug delivery.