In this paper, we theoretically propose a surface plasmon resonance (SPR)-based Dshaped photonic crystal fiber (PCF) sensor with gold coating and an overlayer of molybdenum disulfide (MoS2) 2D material. We design the PCF sensor using the square lattice arrangement of airholes for sensing the analytes of refractive index ranging from 1.33 to 1.42, which includes most of the bio-samples. Further, we optimize the proposed sensor in terms of two different air hole radii, pitch distance, thickness of the gold layer, and 2D material. The details numerical results corroborate that the sensor exhibits a wavelength sensitivity of 20,200 nm/RIU without coating of MoS2 layer. However, it does exhibit an enhanced wavelength sensitivity of 22,800 nm/RIU with a high spectral resolution of 4.38 × 10 -6 RIU when a monolayer of MoS2 is coated onto the gold layer. In addition to wavelength sensitivity, we also compute the amplitude sensitivity and is 752 RIU -1 with a resolution of 1.34×10 -6 RIU. Besides, we carry out the tolerance studies to ensure the robustness of the proposed sensor. Finally, we also analyze the linearity of the sensor through the R 2 value and the same is 0.9688. Thus, the proposed D-shaped MoS2 coated PCF sensor may find potential application in the detection of chemical and biological samples.