Various polymers have been used in drug delivery research as they can effectively deliver the drug to a target site and increase the therapeutic efficacy, while minimizing toxicity. The controlled release of pharmacologically active agents to the specific site at the therapeutically optimal rate and dose regimen has been a major goal on designing such devices. The use of biodegradable polymeric nanofibers as drug carriers can be promising in postoperative local chemotherapy. To develop a drug carrier for cancer therapy, plant polyphenol-loaded polycaprolactone (PCL) nanofibers were fabricated by electrospinning. The resulting nanofibers exhibited a fully interconnected pore structure. ATR-FTIR and XRD results clearly revealed the existence of intermolecular interaction between PCL and polyphenols in nanofibers. The nanofibers showed no burst release and controlled release of polyphenols, which implied the homogenous dispersion and perfect inclusion of polyphenol within the nanofibers. The released polyphenols can generate H2O2, which is the major cause of cytotoxicity of polyphenols. Moreover, generated H2O2 is mainly involved in apoptosis of gastric cancer cells by activation of caspase-3. It is concluded that plant polyphenol-loaded nanofibers are useful in drug delivery to offer a long term cancer therapy and to prevent a recurrence of cancer after surgical operations.