The present study investigated the effect of graphene oxide in cellulose acetate-based composite nanofibers on the transdermal delivery of naproxen. The composite nanofibers were successfully produced via the electrospinning process by directly mixing cellulose acetate, graphene oxide, and naproxen solution with varied compositions. The formation of the nanofibers was confirmed by electron microscopy and other characterization techniques to prove the existence of graphene oxide and naproxen itself. Surprisingly, graphene oxide encourages the production of nanofibers with smaller average diameter, higher conductivity, higher mechanical strength, and higher naproxen release from the cellulose acetate nanofibers. Once combined with naproxen, the composite nanofiber exhibited antibacterial activity with an inhibitory zone of 9.15 mm. The cytotoxicity evaluation also showed that the addition of naproxen increased the death of HeLa cells with a CC50 of up to 29.33 μg mL-1. The kinetic model of naproxen release follows the Korsmeyer-Peppas and Higuchi models with acceleration at neutral pH. These results are promising for further applications for wound healing purposes.