Dextrin and dextrin‐polyethylene oxide (DEX/PEO) fibers in the submicron range were produced by electrospinning of single and blend polymer solutions. The morphology, intermolecular interactions, and mechanical properties of dextrin microfibers with and without PEO were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, X‐ray diffraction, nuclear magnetic resonance spectroscopy, and uniaxial tensile testing. Spectroscopic results confirmed hydrogen bond formation, evidencing dextrin as a molecular entanglement source for fiber mechanical reinforcement. The uniaxial tensile tests demonstrated a synergistic mechanical reinforcement effect that varied with blend composition. Equal weight ratio blends supported a maximum tensile strength with a high elastic modulus and demonstrated to be more elastic and resistant to breaking, even than pristine PEO fibers. Moreover, elastic moduli of blend fiber mats were found to lie within the value range for human skin, thus providing the DEX/PEO meshes with potential applicability as skin tissue scaffolds. This synthesis approach proved the feasible and inexpensive fabrication process of natural‐synthetic polymer hybrid fibers that combine the biocompatibility, biodegradability, and encapsulating capability of dextrin with the mechanical strength and flexibility of PEO for the development of scaffolds for tissue engineering and topical drug delivery applications in skin wound healing. POLYM. ENG. SCI., 59:1778–1786, 2019. © 2019 Society of Plastics Engineers