Tyramine plays a very important role in the proper gastrointestinal function of the human body. By detecting tyramine concentrations, it can be inferred whether the human body is performing normal activities. In this paper, a fiber optic biosensor based on a cladding-offset structure (COF) is proposed to measure tyramine solution at various concentrations.The evanescent field around the probe sensing region is enhanced by etching the probe sensing region with hydrofluoric acid. Due to the large surface area of the gold nanoparticles (AuNPs), likely to occur in the surface chemical reaction, which can be used to capture and recognize tyramine molecules. Therefore, AuNPs are immobilized on the surface of COF to further improve the sensitivity of the tyramine sensor probe. Tyrosinase enzyme is used to enhance the sensitivity of the sensor probe. The performance of the COF fiber sensor is tested by analyzing the transmitted intensity of the sensor. The experimental results demonstrate that the COF-based biosensor provides a good strategy for clinical applications.