This research was aim to develop novel cyclodextrin/chitosan(CD/CS) nanocarriers for insoluble drug delivery through the mild ionic gelation method previously developed by our lab. A series of different bcyclodextrin(β-CD) derivatives were incorporated into CS nanoparticles including hydroxypropyl-bcyclodextrin(HP-β-CD), sulphobutylether-β-cyclodextrin(SB-β-CD), and 2,6-di-O-methy-β-cyclodextrin(DM-β-CD). Various process parameters for nanoparticle preparation and their effects on physicochemical properties of CD/CS nanoparticles were investigated, such as the type of CD derivatives,CD and CS concentrations, the mass ratio of CS to TPP(CS/TPP), and p H values. In the optimal condition,CD/CS nanoparticles were obtained in the size range of 215–276 nm and with the zeta potential from30.22 m V to 35.79 m V. Moreover, the stability study showed that the incorporation of CD rendered the CD/CS nanocarriers more stable than CS nanoparticles in PBS buffer at p H 6.8. For their easy preparation and adjustable parameters in nanoparticle formation as well as the diversified hydrophobic core of CD derivatives, the novel CD/CS nanoparticles developed herein might represent an interesting and versatile drug delivery platform for a variety of poorly water-soluble drugs with different physicochemical properties. This research was aim to develop novel cyclodextrin / chitosan (CD / CS) nanocarriers for insoluble drug delivery through the mild ionic gelation method previously developed by our lab. A series of different bcyclodextrin (β-CD) derivatives were incorporated into CS nanoparticles including hydroxypropyl β-cyclodextrin (SB-β-CD), and 2,6-di-O-methy-β-cyclodextrin (DM-β-CD) preparation and their effects on physicochemical properties of CD / CS nanoparticles were investigated, such as the type of CD derivatives, CD and CS concentrations, the mass ratio of CS to TPP (CS / TPP), and p H values. , CD / CS nanoparticles were obtained in the size range of 215-276 nm and with the zeta potential from 30.22 mV to 35.79 m V. Furthermore, the stability study showed that the incorporation of CD rendered the CD / CS nanocarriers more stable than CS nanoparticles in PBS buffer at p H 6.8. For their easy pre paration and adjustable parameters in nanoparticle formation as well as the diversified hydrophobic core of CD derivatives, the novel CD / CS