A series of biodegradable amphiphilic graft copolymers with poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) as the backbone and poly(2,2-dimethyltrimethylene carbonate) (PDTC) segments with different lengths as the grafted branches were synthesized and characterized. The in vitro degradation of the obtained PHEA-g-PDTC copolymers was studied. With particular branch lengths, PHEA-g-PDTC can form self-assembling micelles in an aqueous solution. Transmission electron microscopy (TEM) images demonstrated that the micelles were regularly spherical in shape. The particle size and distribution of the micelles were measured. Nanoparticle drug delivery systems were prepared by the direct dissolution method. The in vitro release behaviors of two drugs, prednisone acetate and tegafur, with different water solubilities were investigated.