Elevated levels of C-reactive protein (CRP) in the bloodstream are a well-established marker of systemic inflammation in humans. Research on the application of hybrid plasmon material for optical fiber sensor application to sensitively monitor C-reactive protein concentration based on the hybrid material particles has been proposed in this study. Specifically, Au@Ag nanoparticles are coated onto the optical fiber surface by a self-assembled monolayer using an NH2 bridge. CRP antigens are then immobilized onto the surface of Au@Ag NPs to selectively detect CRP and improve sensor sensitivity. The limit of detection for this fiber sensor is 2.4 × 10−5 mg/L. The selectivity of the sensor was also demonstrated in media containing bovine serum albumin (BSA) and glucose. These findings represent an important step toward the development of biosensors capable of monitoring extremely low concentrations of biomolecules in vivo, thereby supporting early disease detection and diagnosis.