We developed an all optic-fiber waveguide-coupled surface plasmon resonance (SPR) sensor using zirconium disulfide (ZrS₂) and poly-dopamine (PDA) as the dielectric layer and biological cross-linker, respectively. This sensor can be employed to monitor the entire process of the C-reactive protein (CRP) sensing, including antibody modification and antigen detection. The design and the optimization of the optical fiber waveguide-coupled SPR sensor were realized, based on the transfer matrix method and first-principles calculations. The sensor was fabricated and characterized according to the optimized parameters. The experimental setup was implemented to measure the entire process of antibody modification and antigen detection for CRP with the detection limit of 3.21 pmol·mL⁻¹, and the specificity tests were also carried out.