Based on the density functional theory, the structure optimization of furanylfentanyl and isofentanyl were performed at the B3LYP/6-311++G(d, p) level, and the Raman spectra were calculated at the same level. Using standard samples, accurate Raman spectra of furanylfentanyl and isofentanyl were obtained experimentally, and the results are in good agreement with the theoretical calculation. The Raman peaks were assigned by PED (potential energy distribution) analysis, the comparison between experimental and theoretical studies shows that the Raman characteristic peaks of furanyfentanyl are 1472, 1003, and 1642 cm^-1, the strongest Raman peak is 1472 cm^-1, while the Raman characteristic peaks of isofentanyl are 1004, 1451, and 1608 cm^-1, the strongest Raman peak is 1004 cm^-1. From the results, it can be seen that the substituent groups of fentanyl have a significant impact on their Raman spectra, which is also the key to distinguishing fentanyl and its analogs. This study provides accurate experimental data and reliable theoretical support for the rapid detection of furanyfentanyl and isofentanyl by Raman spectroscopy, PED analysis provide important reference for the study of the characteristics of Raman spectra of fentanyl and its analogs, which will contribute to the development of Raman detection standards for fentanyl New Psychoactive Substances and the establishment of drug Raman spectroscopy databases.