New, biodegradable poly(L-lactide) disulfides, PLLA-SS-PLLA, were first prepared through the DMAP-catalyzed ring-opening polymerization of L-lactide with a dihydroxyethyl disulfide initiator, and were further catalytically reduced into thiol-end-functionalized poly(L-lactide)s, HO-PLLA-SH, with a tributyl phosphine catalyst (PBu3). Employing the HO-PLLA-SH as the ligand, new core-shell CdSe/PLLA quantum dots (QDs) were continuously prepared via a facile ligand-exchanging process with the CdSe/TOPO QD precursor. The chemical structures, morphologies and solvent solubility of these prepared CdSe/PLLA QDs were investigated by NMR spectroscopy, FTIR spectroscopy, XRD, TEM and excitation under either room light or UV radiation at 365 nm, demonstrating the successful ligand replacement and the new formation of core-shell CdSe/PLLA QDs (diameter:4.0 +/- 0.3 nm). Finally, UV and FL results indicate the two factors of the HO-PLLA-SH ligand molecular weight and the ligand/QD precursor feeding weight ratio were important for preparing stable and highly photoluminescent CdSe/PLLA QDs.