Periodontitis is an economically important disease which is highly prevalent worldwide. Current diagnostic approaches are time-consuming and require interpretation of multiple aspects of clinical and radiographic assessment. Chair-side monitoring of inflammatory mediators of periodontitis could provide immediate information about disease activity, which can inform patient management. We aimed to develop a novel prototype biosensor to measure salivary matrix metalloproteinase-8 (MMP-8) using specific antibodies and surface acoustic wave (SAW) technology. The analytical performance of the prototype biosensor was compared to standard enzyme-linked immunosorbent assay (ELISA) using unstimulated saliva samples obtained from patients with periodontitis before and after non-surgical treatment (N = 58), patients with gingivitis (N = 54) and periodontally healthy volunteers (N = 65). Receiver operator characteristic (ROC) analysis for distinguishing periodontitis from health revealed an almost identical performance between the sensor and ELISA assays (area under curve values (AUC): ELISA 0.93; SAW 0.89). Furthermore, both analytical approaches yielded readouts which distinguished between heath, gingivitis and periodontitis, correlated identically with clinical measures of periodontal disease and recorded similar post-treatment decreases in salivary MMP-8 in periodontitis. The assay time for our prototype device is 20 minutes. The prototype SAW biosensor is a novel and rapid method of monitoring periodontitis which delivers similar analytical performance to conventional laboratory assays.