In this paper, an enhanced optical fiber biosensor based on nanomaterials is proposed for the detection of enrofloxacin residues in food. Single mode fiber (SMF), multimode fiber (MMF), and four-core fiber (FCF) were fused to fabricate an SMF-MMF-FCF-MMF-SMF fiber structure. Then, a three times tapered (T3) optical fiber structure was fabricated on FCF. The WaveFlex fiber structure T3-SMF-MMF-FCF-MMF-SMF was fabricated. The optical fiber surface was modified with gold nanoparticles, zinc oxide nanowires (ZnO-NWs), and Fe 3 O 4 and Au nanocomposites to stimulate and enhance the localized surface plasmon resonance (LSPR) effect. The enrofloxacin monoclonal antibody was fixed on the surface of the probe in order to achieve specific differentiation detection. The performance of the sensor was verified by testing 0−1000 μg/mL enrofloxacin solutions. The sensitivity of the proposed sensor is 1.89 nm/ ln (μg/mL), with a detection limit (LoD) of 0.16 μg/mL. In addition, the method has good reproducibility, reusability, repeatability, stability, and selectivity. It has also obtained promising results in real environment (milk, juice, pork, and chicken) tests and can be used for the detection of enrofloxacin in food.