In this paper, a D-shaped surface plasmon resonance (SPR) refractive index (RI) based biosensor is reported for the earlier detection of various bio-analytes. The lattice of D-shaped photonic crystal fiber (PCF) offers a modified rhombus pattern for cladding air holes. D-shaped PCF is an open channel structure that fundamentally provides ease while interacting with different bio-analytes as compared to closed channels SPRs. A nanoscale MXene (Ti3C2Tx) layer is introduced with a uniform coating that drastically enhances the sensor's sensitivity and performance. Finite element method (FEM) is employed to determine dispersion characteristics to acquire the confinement loss spectra as a function of wavelength for various bio-analytes. SPR shifts the resonant interference dip when RI of bio-analytes changes. The proposed SPR sensor with Au/ Ti3C2Tx layer exhibits maximum RI sensitivity of 47,260 nm/RIU at an analyte refractive index of 1.42 with a detection resolution of 2.11 x 10−6 RIU, which is 1.7 times higher than that of a single Au-layer SPR sensor. Moreover, it detects a wider range of bio-analytes (i.e., 1.30–1.43) using a third-order polynomial fitting function corresponding to the wavelength shift. It covers the detection of most known bio-analytes, i.e., cancerous cervical, breast and blood cells, adrenal gland, glucose concentration, proteins, viruses or DNA/RNA, etc.