Herein, novel hybrid nanomaterials were developed for wound dressing applications with antimicrobial properties. Electrospinning was used to fabricate a double layer nanocomposite nanofibrous mat consisting of an upper layer of poly(vinyl alcohol) and chitosan loaded with silver nanoparticles (AgNPs) and a lower layer of polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP) nanofibers loaded with chlorhexidine (as an antiseptic). The top layer containing AgNPs, whose purpose was to protect the wound site against environmental germ invasion, was prepared by reducing silver nitrate to its nanoparticulate form through interaction with chitosan. The lower layer, which would be in direct contact with the injured site, contained the antibiotic drug needed to avoid wound infections which would otherwise interfere with the healing process. Initially, the upper layer was electrospun, followed sequentially by electrospinning the second layer, creating a bilayer nanofibrous mat. The morphology of the nanofibrous mats was studied by scanning electron microscopy and transmission electron microscopy, showing successful nanofiber production. X-ray diffraction confirmed the reduction of silver nitrate to AgNPs. Fourier transform infrared spectroscopy showed a successful incorporation of the material used in the produced nanofibrous mats. Thermal studies carried out by thermogravimetric analysis indicated that the PVP-drug-loaded layer had the highest thermal stability in comparison to other fabricated nanofibrous mats. Antimicrobial activities of the as-synthesized nanofibrous mats against , , , and were determined using disk diffusion method. The results indicated that the PEO-drug-loaded mat had the highest antibacterial activity, warranting further attention for numerous wound-healing applications.