Recently, unique structure fiber enacts a significant role in sensing applications. A novel D-shaped negative curvature fiber based surface plasmon resonance (SPR) sensor is proposed. The design consists of negative curvature solid core fiber surrounded by a cladding composed of double-layer adjoined airholes. An outside layer of the cladding contains semi-circular airholes, and the interior layer has small circular air holes to overwhelm the higher-order modes. The external sensing approach detects changes in the refractive index between 1.33 and 1.37. Employing gold as a plasmonic material, SPR is developed on top of the photonic crystal fiber (PCF). Between the gold layer and the PCF, a small layer of titanium dioxide is placed for binding the plasmonic material to the fiber. And it acts as an adhesive layer. The finite element method is used to perform numerical analyses. After improving the structural parameters, an enhanced sensitivity of 26 000 nm RIU−1 is achieved. Because of its enhanced sensitivity, this sensor is used in a bio-medical application to detect and prevent diseases in the early stage.