Genistein is a phytochemical with a broad range of desirable biological activity for wound healing. However, its poor bioavailability requires developing a new method for fabricating an appropriate carrier vehicle to deliver genistein in a sustained manner. Based on the guidance afforded by the ternary phase diagram of poly(D,L-lactic acid) (PDLLA), poly(ethylene oxide) (PEO), and genistein blends, certain selective compositions were electrospun. We obtained a uniformly smooth surface morphology in unmodified and genistein-modified PEO/PDLLA fibers, documented by scanning electron microscopy. Moreover, wide-angle X-ray diffraction and 1H NMR studies revealed that the genistein molecules, successfully incorporated in the blends, remained chemically stable after electrospinning. Besides surface wettability and dimensional stability of the electrospun mats, the released genistein amount has been evaluated as a function of PEO concentration. Our biocompatibility investigations suggest that genistein-modified PEO/PDLLA electrospun mats exhibit strong antioxidant and anti-inflammatory activities which indicate they have potential applications for wound dressings.