In this study, gas chromatography-mass spectrometry (GC-MS) following microwave distillation and solid-phase microextraction (MD-SPME) was developed for the analysis of essential oil compounds in Nepeta crispa. To improve the headspace (HS) method, microwave powers, irradiation times, and SPME fiber coatings were studied. The optimal experiment parameters obtained were 65-μm PDMS/DVB SPME fiber, a microwave power of 400 W, and an irradiation time of 3 min. MD-SPME was compared with headspace solid-phase microextraction (HS-SPME) and conventional hydrodistillation (HD) for the extraction of essential oil compounds in N. crispa. A comparative qualitative and quantitative study on the composition of the oils was carried out. For this, 26 compounds, constituting 98.2% of the oil, were identified in the essential oil by MD-SPME, and 23 compounds, representing 91.3% of the oil, were characterized in the SPME and HD methods; 25 compounds, constituting 94.6% of the oil, were separated and identified. The main compounds identified by all methods were 1,8-cineol, β-bourbonene, α-terpineol, and β-pinene. The relative standard deviation (RSD) values of less than 8% show that the MD-SPME method has good repeatability.It has been shown that the extraction of essential oils from N. crispa with MD-SPME was better in terms of energy saving, extraction time, plant material, oxygenated fractions, and product quality.