An effective bio-sensing platform that would meet the criteria of rapid, simple, and sensitive detection is crucial to translate bench research to clinical applications. However, simultaneously rapid and sensitive biosensing remains challenging for practical biomedical applications. In this study, for the first time, we demonstrate a cost-effective, label-free, real-time, and sensitive slab waveguide-based particle plasmon resonance (WGPPR) biosensor for practical clinical applications. A suspended glass slab waveguide structure with excellent optical confinement properties was designed and fabricated as the biosensor. Gold nanoparticles (AuNPs) were deposited on the top surface of the waveguide layer to significantly enhance the optical near field through the localized surface plasmon resonance (LSPR) effect. When light travels through the waveguide, the change in the local refractive index (RI) near the surface of the AuNPs can be transformed into changes in the intensity of transmitted light, thereby enabling sensitive and real-time detection. The RI sensing experiment shows a good sensor resolution of 1.43 × 10-4 RIU, which represents a 395% enhancement compared to that of the sensor without AuNPs. Through biochemical detection experiments, we measured IgG and determined the detection limit (LOD) at 614 ng mL-1 in ∼4 min, thereby proving the feasibility of the bio-detection sensing functionality. This study demonstrates a new type of WGPPR biosensor, which offers several unique advantages such as simple structure, high sensitivity, and rapid bio-sensing for practical bio-medical sensing applications. The new biosensor also fulfils point-of-care (POC) requirements.