In this research, the fabrication of nanocomposite films consisting of cellulose acetate (CA), pristine and modified halloysite nanotubes (mHNTs), and curcumin was investigated by solution casting method for wound dressing applications. The chemical structure, morphology, and surface properties of the samples were studied by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and contact angle measurement. Furthermore, the effects of modified halloysite nanotube were examined on mechanical properties, water vapor transmission rate (WVTR), and curcumin release. The results revealed that mHNTs enhanced mechanical strength and hydrophilicity, as well as it increased curcumin release, and controlled its release rate, which this could be attributed to the high activity of terminal groups (amine) comparing to pristine halloysite nanotubes (HNTs). Moreover, better adhesion and integrity between the nanoparticles and polymeric matrix were confirmed by enhancement in mechanical strength. The cell proliferation assay also indicated the biocompatibility and nontoxicity of the samples and their potential of being an appropriate substrate for cell adhesion.