Biodegradable and amphiphilic poly(L-lactide)-b-poly(ethylene oxide) copolymers with different arms (PLLA-b-PEO having one, two, four, and six arms) were successfully synthesized via a two-step synthetic strategy. The hydrophilicity-hydrophobicity balance of these copolymers was mainly controlled by both the arm number of copolymers (i.e., macromolecular architecture) and the poly(ethylene oxide) (PEO) composition. Biodegradable nanoparticles could be generated by direct injection of these PLLA-b-PEO copolymers solutions into distilled water, and their critical micelles concentrations decreased with the increasing arm number of copolymers. Moreover, both the hydrophilic PEO composition and the arm number of copolymers controlled the average size of PLLA-b-PEO nanoparticles, and the nanoparticles with adjustable sizes (20-85 nm) completely meet the size prerequisite (less than 100 nm) for targeted drug delivery. In vitro degradation of PLLA-b-PEO nanoparticles showed that the PLLA composition gradually increased over the degradation time, and the degree of crystallinity of PLLA block within copolymers increased simultaneously. Furthermore, the nimodipine drug loading efficiency of the PLLA-b-PEO copolymers was apparently higher than that of PLLA homopolymers. The drug-release experiments demonstrated that these biodegradable nanoparticles might be used for a short-time controlled release system. Consequently, this will provide a facile method not only to design new PLLA-based biomaterials from both the macromolecular architecture and the hydrophilicity-hydrophobicity balance, but also to fabricate biodegradable nanoparticles with adjustable sizes for drug delivery.