Amphiphilic hyperbranched polyglycerols (HbPG) were synthesized by dodecyl and octadecyl alcohols as direct initiators for the ring-opening multibranching polymerization of glycidol. These polymers possess molecular weight dependent surface activity, and are efficient surfactants and stabilizers for poly(lactic/glycolic acid) (PLGA) nanoparticles, opening new possibilities for functionalized drug carriers, targeting, imaging agents, etc.