The main attitude of new wound dressings with biocompatible natural or synthetic polymers is improving and accelerating the healing process. In this study, halloysite nanotubes (HNTs) loaded with a model antibiotic drug, amoxicillin (AMX), were incorporated within poly(lactic-co-glycolic acid) (PLGA) solution that were electrospun with hydrophilic chitosan nanofibers simultaneously in two different syringes to make composite nanofibrous mat. The morphology, homogeneity, and fiber diameter of electrospun (PLGA/HNTs/AMX/chitosan) composite nanofibers were investigated by scanning electron microscopy and image J software. To evaluate the chemical structure, mechanical property, contact angle, and water absorption of samples, Fourier transform infrared spectroscopy, tensile testing, water contact angle, and immersion in phosphate buffer saline were utilized, respectively. Results indicated that incorporation of HNTs does not significantly alter nanofibers' morphology but rather increases their diameter, while the mechanical properties are improved because of its high modulus. Also, addition of natural hydrophilic polymer nanofibers (chitosan) enhanced the hydrophilicity property of samples. According to high-performance liquid chromatography drug release analysis, HNTs as a good nanocarrier decreased initial burst release and showed controlled release behavior. MTT assay determined biocompatibility of PLGA/HNTs/AMX/chitosan. Copyright (C) 2016 John Wiley & Sons, Ltd.