Chitosan oligosaccharides graft polycaprolactone copolymer (PHCSO-g-PCL) has been synthesized via initiating the polymerization of e-caprolactone (CL) monomer through an amino group protection route using phthaloyl chitosan oligosaccharide (PHCSO) as intermediate. The grafting reaction was carried out in Pyridine at 120°C with the hydroxyl group of the chitosan oligosaccharide (CSO) as initiator and the tin 2-ethylhexanoate (Sn (Oct)2) as catalyst. The PHCSO-g-PCL nanoparticles with and without bovine serum albumin (BSA) drug were prepared through the self-assembled approach in Dimethylformamide (DMF) organic solvents. PHCSO-PCL copolymer was investigated by Fourier transform infrared spectroscopy (FTIR), 1H NMR spectrum and scanning electron microscopy (SEM). The physicochemical properties of the hydrophobized PHCSO-g-PCL nanoparticles were characterized by fluorescence spectroscopy and dynamic light scattering (DLS). The results of DLS showed that the hydrodynamic diameters and particle size distribution with various concentrations of PHCSO-g-PCL nanoparticles were from 69.82 nm to 195.9 nm with a narrow polydispersity factor of 0.212 to 0.172. The results of DLS also showed that the hydrodynamic diameters and particle size distribution of PHCSO-g-PCL (5 mg/ml) nanoparticles without and with BSA drug (0.4 mg/ml) were from 168.44 nm to 200.7 nm. The polydispersity factor was from 0.119 to 0.159.