In this work, the high-quality factor (Q-factor) and high sensitivity of a circular substrate-integrated waveguide (CSIW) are proposed for the characterization of semisolid materials. The modeled sensor was designed based on the CSIW structure with a mill-shaped defective ground structure (MDGS) to improve measurement sensitivity. The designed sensor oscillates at a single frequency of 2.45 GHz, which was simulated using an Ansys HFSS simulator. Electromagnetic simulation explains the basis of the mode resonance of all two-port resonators. Six variations of the materials under test (SUTs) were simulated and measured, including air (without an SUT), Javanese turmeric, mango ginger, black turmeric, turmeric, and distilled water (DI). A detailed sensitivity calculation was performed for the resonance band at 2.45 GHz. The SUT test mechanism was performed using a polypropylene tube (PP). The samples of dielectric material were filled into the channels of the PP tube and loaded into the center hole of the MDGS. The E-fields around the sensor affect the relationship with the SUTs, resulting in a high Q-factor value. The final sensor had a Q-factor of 700 and a sensitivity of 2.864 at 2.45 GHz. Due to the high sensitivity of the presented sensor for characterization of various semisolid penetrations, the sensor is also of interest for accurate estimation of solute concentration in liquid media. Finally, the relationship between the loss tangent, permittivity, and Q-factor at the resonant frequency were derived and investigated. These results make the presented resonator ideal for the characterization of semisolid materials.