In this study, high-performance liquid chromatography and terahertz time-domain spectroscopy were used to experimentally detect metronidazole analytical pure and oral metronidazole. Based on various exchange-correlation function models of density functional theory, the molecular vibration frequencies of metronidazole in the terahertz band were calculated, and the characteristic absorption peaks of metronidazole were identified. The experimental results show that the results of terahertz time-domain spectroscopy are in good agreement with those of high-performance liquid chromatography, and terahertz time-domain spectroscopy can quickly detect drug residuals. The positions of the characteristic absorption peaks of metronidazole obtained via terahertz time-domain spectroscopy are very close to the calculated values, which indicates that the metronidazole molecular vibration frequency is in the measurable range of the system, and the formation mechanism of the characteristic absorption frequency is similar to the vibration mode of the molecular group. This research has important reference value for the applications of rapid detection of antibiotic drugs and the identification of active ingredients in compounds.