A large variety of amphiphilic polylactide-grafted dextrans has been synthesized with controlled architecture through a three-step procedure: partial protection of the dextran hydroxyl groups by silylation; ring-opening polymerization of D,L-lactide initiated from remaining hydroxyl groups on partially silylated dextran; and silyl ether deprotection under very mild conditions. Throughout the synthesis, detailed characterizations of each step led to the control of copolymer architecture in terms of graft number and lengths of graft and backbone. Depending on their proportion in polylactide, these copolymers were either water-soluble or soluble in organic solvents. The potential of these amphiphilic grafted copolymers as surfactants was estimated. Their organization at air/water or dichloromethane/water interfaces was investigated by interfacial tension measurements. Self-organization in water or toluene was evaluated using fluorescence spectroscopy. Depending on its solubility, each copolymer showed noticeable surfactant properties and was able to produce either hydrophobic or hydrated microdomains in water or toluene solutions, respectively.