The aim of this work was to determine the potential of using a pulsed electric field (PEF) and ultra-sound (US) apparatus to produce mitragynine extracts from Mitragyna speciosa dried leaves. Four modes of the device were tested: PEF, US, US + PEF, and PEF + US. The results were compared with extracts obtained using a conventional technique (maceration, as the control). Changes in the mitragynine content were determined with the liquid chromatography/mass spectrometry (LC-MS/MS) method. The LC-MS/MS analysis showed that the mitragynine contents from kratom extracts using four different modes were different. The highest extraction (106.63 ± 0.85 mg/L) of mitragynine was achieved by the PEF + US procedure, followed by US + PEF (97.27 ± 1.33 mg/L), with increased extraction efficiencies of 45.81 ± 0.59% and 33.00 ± 1.85%, respectively. Moreover, the total energy consumption under the combination technique was 25.0% lower than that with PEF assistance. Furthermore, scanning electron microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) provided confirmatory evidence for the extraction of M. speciosa by the prototype. This study confirmed that PEF and US devices can be considered a green alternative method and may contribute to the application of agricultural products.