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Thiol-containing natural products possess a wide range of bioactivities. The burst of synthetic biology technology facilitates the discovery of new thiol-containing active ingredients. Herein, we report a sensitive, quick, and robust surface-enhanced Raman scattering technology for specific and multiplex detection of thiol-containing compounds without purification requirements and also indicating the thiols with different chemical environments. Using this platform, we successfully demonstrated the simultaneous detection of thiol-containing