The synthesis of water soluble star-block copolypeptides and their encapsulation properties are described. The star-block copolypeptides, obtained by ring-opening polymerization of amino acid N-carboxyanhydrides, consist of a PEI core, a hydrophobic polyphenylalanine or polyleucine inner shell, and a negatively charged polyglutamate outer shell. The encapsulation study showed that these water soluble, amphiphilic star-block copolypeptides could simultaneously encapsulate versatile compounds ranging from hydrophobic to anionic and cationic hydrophilic guest molecules.