This paper presents two different types of sensors that are based on the matryoshka geometry with a Defected Ground Structure (DGS). The main idea is to compare the sensor’s response for close and open matryoshka rings. The proposed DGS sensor geometry is outlined, and initial design equations are presented. Two prototypes were fabricated and characterized. Very good agreement is obtained between numerical simulation and experimental results for the open configuration. Moreover, the resonance frequency determined using the proposed design equations presents a good agreement too. To verify the matryoshka DGS sensors’ response, a mixture of distilled water and isopropyl alcohol was characterized, and the corresponding calibration curves are compared. Finally, the matryoshka DGS sensors, are compared also in terms of miniaturization and sensitivity.