A novel, to the best of our knowledge, optimized structure is proposed to enhance the sensitivity of a surface plasmon resonance (SPR)-based biosensor for urine glucose detection by adding a few layers of black phosphorous (BP) (two-dimensional material) over the zinc oxide (ZnO) sandwiched in between gold (Au) and silver (Ag) bimetallic layers. Results show that with an optimized thickness of 42 nm/Au, 12 nm/ZnO, .05 nm/Ag, and 2.65 nm/BP, the sensitivity of 289°/RIU can be achieved at a 633 nm operating wavelength. This is enhanced up to 1.5 times from the conventional biosensor. It is further enhanced up to 3 times with the addition of five numbers of BP sheet layers (each sheet has a thickness of 0.53 nm) over the Au/ZnO/Ag layers, as BP possesses a high absorption coefficient at the incident wavelength of 633 nm. This biosensor is rather efficient at responding to the minute change of 0.001 in the refractive index of urine samples for non-diabetic persons (0–15 mg/dL) and diabetic persons (0.625 gm/dL, 1.25 gm/dL, 2.5 gm/dL, 5 gm/dL, and 10 gm/dL) with the corresponding refractive indices of 1.335, 1.336, 1.337, 1.338, 1.341, and 1.347. It provides significant resonance shift and higher sensitivity in terms of changes in the resonance angle shift. This proposed work has the potential to detect glucose concentration levels with higher accuracy and with faster sensor responses.