The stabilization of size-specific monodisperse CdS nanoclusters has received much attention. However, the development of matrices, e.g., polymers micelles, zeolites, for this purpose has remained largely empirical. Here a combinatorial and informatics approach to the discovery of ligands for CdS nanocluster stabilization is introduced It is shown that combinatorially derived peptide and peptidomimetic ligands based on phytochelatins can stabilize CdS nanoclusters and that an informatics analysis of the library used design parameters critical for obtaining second-generation ligands.