Detection of biomarkers for tracking disease progression is becoming increasingly important in biomedicine. Using saliva as a diagnostic sample appears to be a safe, cost-effective, and non-invasive approach. Salivary interleukin-8 levels demonstrate specific changes associated with diseases such as obstructive pulmonary disease, squamous cell carcinoma, oral cancer, and breast cancer. Traditional protein detection methods, such as enzyme-linked immunosorbent assay (ELISA), mass spectrometry, and Western blot are often expensive, complex, and time-consuming. In this study, an optical fiber-based biosensor was developed to detect salivary IL-8 protein in a label-free manner. The biosensor was able to achieve an ultra-low limit detection of 0.91 fM. Moreover, the tested concentration range was wide: from 273 aM to 59 fM. As a proof-of-concept for detecting the protein in real clinical samples, the detection was carried out in artificial saliva. It was possible to achieve high sensitivity for the target protein and minimal signal alterations for the control proteins.