In this paper, the novel carboxymethyl-p-cyclodextrin grafted chitosan (CMCD-g-CS) nanoparticles were fabricated and their potential as oral delivery carrier of protein drugs was evaluated. The physicochemical properties of the prepared nanocarriers were characterized by Fourier transforms infrared spectroscopy, nuclear magnetic resonance, transmission electron microscopy and dynamic light scattering. Bovine serum albumin (BSA), a model protein drug, was loaded in prepared nanocarriers with ideal entrapment efficiency (EE) and loading content (LC). The drug release profiles of BSA loaded nanoparticles were studied in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). It was found that the drug loaded nanovehicles displayed a typical controlled sustained release profiles and the amount of BSA released from the nanocarriers was much higher in SIF and SCF than it in SGF. The research results suggested that the CMCD-g-CS nanoparticles had the potential as promising nanocarriers for oral delivery of protein drugs.