Periodontal disease (PD) is a chronic condition associated with systemic risks like cardiovascular disease and diabetes. Traditional diagnostics detect advanced PD but often miss early‐stage cases, where timely intervention is critical. Oral polymorphonuclear neutrophils (oPMNs) are emerging as key biomarkers for periodontal health. This study presents DePerio, an AI‐driven deep neural network (DNN) method that isolates and quantifies oPMNs from saliva using their natural hydrophilic adhesion on treated surfaces. Trained on thousands of annotated bright‐field images, DePerio accurately detects and counts oPMNs within milliseconds. Validation against standard techniques confirms its precision in measuring oral inflammatory load (OIL). Clinical testing on 51 samples from healthy and periodontitis patients demonstrates DePerio's capability to distinguish five OIL levels, assisting in PD severity assessment. This low‐complexity, AI‐powered tool offers a rapid, reliable approach for early PD detection and management in dental practices.

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Recent research has identified salivary oral polymorphonuclear neutrophils (oPMNs) as reliable cellular biomarkers for monitoring the progression of periodontal disease (PD). While conventional diagnostic tools such as periodontal probing and radiographic imaging are effective at detecting advanced disease stages, they lack the sensitivity required for early diagnosis. oPMNs, derived from circulating white blood cells (WBCs), transmigrate through the oral epithelium and appear in saliva with diverse morphological characteristics. Although deep learning-based WBC quantification has been extensively explored using peripheral blood datasets, the unique morphology of oPMNs necessitates the development of new image datasets and retraining of models tailored to their detection. To address these challenges, we introduce DePerio-an AI-powered diagnostic pipeline that integrates a novel oPMN isolation protocol with deep neural network (DNN) architectures. We evaluate the performance of multiple DNN models to achieve accurate detection and quantification of oPMNs. Validated against standard quantification methods for oPMNs and oral inflammatory load (OIL), DePerio achieved a detection error rate of less than 5%. In a clinical study involving 111 human saliva samples, spanning individuals from healthy to severe periodontitis cases, and successfully classified five distinct OIL levels. This robust and low-complexity platform provides a scalable and practical solution for early PD detection and longitudinal monitoring in clinical dental practice.