Recently, preparation and screening of compound libraries remain one of the most challenging tasks in drug discovery, biomarker detection, and biomolecular profiling processes. So far, several distinct encoding/decoding methods such as chemical encoding, graphical encoding, and optical encoding have been reported to identify bioactive peptide ligand from those libraries. For peptide library encoding, we have developed simple and efficient surface-enhanced Raman scattering (SERS) based encoding method on PEG resin beads for multiplexed high-throughput screening (HTS) system, which involves highly sensitive SERS dots (so called SERS ID) [1]. The 44 kinds of SERS IDs were able to generate simple codes and could possibly generate more than one million kinds of codes by incorporating combinations of different SERS IDs. The barcoding method exhibited high stability and reliability under bioassay conditions. Using the SERS ID encoding based screening platform, we can identify the on-bead bioactive peptide ligands, and at the same time, quantify its binding affinity for specific protein. The advantages of this SERS dots based encoding method lies in the availability of a large number of Ramam active molecules which can be utilized as Raman label compounds. Moreover, the SERS signals have narrow band width (< 2 nm) without peak overlap, and a single excitation is used for the detection of multiple encodings. We believe that our SERS barcoding technology is a promising method in the screening of one-bead-one-compound (OBOC) libraries for drug discovery.