In the dental medical field, an infection of opened oral tissues by bacteria give rise to serious periodontal disease (PD) after trauma or various oral surgery such as third molar extraction, oral implant, and unexpected trauma. However, progress for bioactive improvement, a prevention of oral tissue contamination, has been currently limitation. Therefore, an innovative research is extremely important and needed for immediately inhibition of bacteria. In this study, we designed a biocompatible oral wound dressing as co-electrospun nanofiber to combine gelatin (GE) and polyurethane (PU) containing silver nanoparticle (AgNPs) to enhance antibacterial activity targeting to periodontal bacteria. Prior to an electrospinning (ELSP), AgNPs was directly synthesized by silver nitrate with capping agent within dimethylformamide (DMF) for use as an ELSP solvent. The fabricated products were cross-linked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) followed by characterized via theoretical analysis. In results, AgNPs were not only perfectly synthesized without a reduction agent, but also electrospun nanofiber (EN) containing AgNPs was well fabricated with the modulation of AgNPs levels. Additionally, the presence of AgNPs within the fiber strand was clearly shown. In the antibacterial test, the developed oral wound dressing showed excellent antibacterial activity as increasing content of the AgNPs. All of tests clearly confirmed that our strategy may suggest a useful paradigm as oral wound dressing to prevent of a bacterial infection as means to oral wound dressing of gingiva and periodontal tissues for obviation of periodontitis.