Extraction of Clinacanthus nutans (Burm.f.) lindau (C. nutans) or Phayayo (PY) leaves was performed by maceration using ethanol as an extractant. The antioxidant activity was evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. The inhibitory concentration at 50% antioxidant activity (IC50) of PY extract was 15.62 mg/mL. The electrospun cellulose acetate (CA) nanofibers containing PY extract at concentrations of 2.5, 5, and 7.5% w/v and silver (Ag) nanoparticles at 0.1% w/v were fabricated. The addition of PY extract and Ag influenced the viscosities of solutions and therefore affected the morphology and fiber diameters. The electrospun CA fiber mat containing 0.1% Ag and 7.5% PY extract was chosen to investigate its potential for use in wound dressing applications. The degrees of weight loss and water swelling of the electrospun CA/PY7.5/Ag fiber mat after immersion in a phosphate buffer solution (pH 7.4) at 37°C were examined in a range of 2-24 h, and found to increase with immersion time. The antioxidant activity of the fiber mat at the same period of immersion time was also studied, which corresponded with the trends of weight loss and water swelling. The antioxidant activity at 24 h of immersion was 68.3±9.2%. The CA/PY7.5/Ag fiber mat had no antibacterial activity against Escherichia coli but slightly inhibited the growth of Staphylococcus aureus. The fiber mat also possesses high hydrophilicity, as examined by the contact angle measurement. These results indicate that the CA/PY7.5/Ag fiber mat is a promising material for use as a topical transdermal patch or wound dressing.