This work presents a high-performance surface plasmon resonance (SPR)-based biosensor for glucose detection. While adding a metal-organic framework (MOF) layer, UiO-66, to the biosensor improves selectivity and enables direct detection without additional receptors, it does not significantly enhance sensitivity. A SPR-based biosensor is proposed to overcome this limitation by introducing a layer of 2D-transition metal dichalcogenides (2D-TMD) and decorating the UiO-66 structure with gold nanoparticles (UiO-66AuNP). The optical properties of the biosensor for glucose detection in urine are investigated by employing the finite difference time domain (FDTD) method with Kretschmann configuration at a wavelength of 633 nm, and its performance is effectively improved by incorporating 2D-TMD and AuNP layers into the biosensor structure. Notably, the SPR-based biosensor with the decorated UiO-66 layer exhibits a further change in the SPR angle in the presence of glucose-containing urine. Using computational studies, various performance parameters, such as the biosensors' signal-to-noise ratio (SNR) and quality factor (QF), are evaluated in addition to sensitivity. The maximum sensitivity achieved is 309.3°/RIU for the BK7/Ag/PtSe2/WSe2/MoS2/UiO-66AuNP/sensing medium structure. The exceptional performance of the proposed biosensor structure demonstrates its suitability for precise glucose detection in urine while also opening new avenues for developing bioreceptor-free SPR-based sensors.