Combinatorial homoserine lactone mixtures and individual products were obtained from the methionine-functionalized resin in solid-phase synthesis. The four-step process consisting of a coupling step of an N-Fmoc-L-methionine, deprotection of N-Fmoc group, N-coupling with a carboxylic acid, and cleavage reaction through a polymer supported strategy is described. Gas chromatography-mass selective detector (GC-MSD) techniques provide the most powerful methods for identifying both the combinatorial mixtures and individual products.