Chronic wounds have become a major health problem worldwide. Curcumin (Cur), with strong anti-inflammatory and anti-infective properties, is introduced as a unique molecule for wound dressing applications. In the present study, Cur-loaded chitosan/poly­(ethylene oxide)/collagen (Cho/PEO/Col) nanofibers were developed for wound dressing applications by the blend–electrospinning process. Structural, mechanical, and biological properties of nanofibers were evaluated using SEM, FTIR, tensile testing, in vitro release study, Alamar blue cytotoxicity assay, and in vivo study in a rat model. According to the results, Cur was successfully released up to 3 days without any significant cytotoxicity of the above hybrid to human dermal fibroblasts. In vivo studies on full-thickness wounds in the rat model indicated significant improvement in the mean wound area closure by applying Cur-loaded Cho/PEO/Col nanofibers. The electrospun Cho/PEO/Col nanofibers loaded with Cur could be considered as a promising type of wound dressing in the wound-healing process.