In this study, we report the Raman spectroscopy of etomidate and its analogs medetomidate, propoxate, and the metabolite etomidate acid, and the spectroscopy was analyzed in conjunction with quantum chemical calculations. The results demonstrate distinct Raman spectroscopy differences between etomidate acid and etomidate, due to structural differences, etomidate, medetomidate and propoxate exhibit significantly different Raman activities in the regions of 691～715, 842～866, 955, 1 351～1 375, and 1 411～1 453 cm^-1, which are the key to differentiate the three substances. The investigation further compares the Raman spectroscopy of etomidate and its analogs with those of New Psychoactive Substances(NPS), including piperazine, fentanyl, and cathinone. Potential energy distribution (PED) analysis identifies characteristic Raman peaks near 923, 980, 1 000, 1 030, 1 710, and 1 360 cm^-1 are identified as key indicators for recognizing etomidate and its analogs. Finally, the suspected etomidate “smoke powder” seized by the public security department is tested, and its etomidate content is rapidly confirmed through Raman spectroscopy. The study provides an important reference for the rapid detection of etomidate and its analogs, and also systematically analyzes the differential Raman spectroscopy of etomidate, medetomidate, propoxate and etomidate acid, which makes it possible to differentiate etomidate and its analogs by Raman spectroscopy.