Bombyx mori silk fibroin (BMSF), a natural protein polymer, has increasingly gained research interest as promising biomaterial in drug delivery application due to its excellent biological and physiochemical properties. In this study, antibiotic loaded silk/PVA core-shell nanofibers has been prepared followed by surface modification using homogeneous oxygen (O-2) dielectric barrier discharge (DBD) plasma at atmospheric pressure. Polyvinyl alcohol (PVA) is used as the shell material whereas amoxicillin trihydrate is loaded into the silk solution (AMOXBMSF) and the mixture is used as core material for fabricating core-shell nanofibers. O-2 DBD plasma treatment induces surface hydrophilicity in AMOX-BMSF/PVA nanofibers due to incorporation of polar functional groups onto the surface as revealed from X-ray photoelectron spectroscopy (XPS) analyses. The O-2 DBD plasma treatment facilitates formation of hydrogen bonds on the surface of the nanofibers resulting in better mechanical behavior of the nanofibers. The DBD plasma treated nanofibers show relatively faster biphasic drug profile than the untreated nanofibers with prolonged antibacterial activities against Gram-negative Escherichia coll. and Grampositive Staphylococcus aureus bacteria. The results demonstrate that O-2 DBD plasma surface modified AMOXBMSF/PVA nanofibers can be explored as mechanically enhanced wound dressing in treatment of skin and wound Infections.