Diabetes and periodontitis, as widespread chronic diseases, often exacerbate each other's conditions. Nonsurgical periodontal treatments can improve the oral and systemic health in these patients, with salivary proteins offering potential insights into disease mechanisms and treatment effectiveness. However, there is a lack of comprehensive data on salivary proteomics in this context. By assigning patients with diabetes-associated periodontitis to a test group (supragingival scaling, subgingival scraping and root planing) or a control group (supragingival scaling only), analyzing nonstimulated whole saliva samples using liquid chromatography-tandem mass spectrometry, and establishing the in vivo and in vitro models, we found significant differential expression of salivary proteins related to Apelin signaling pathway, hematopoietic cell profiling, stress response and immune regulation, identifying four candidate proteins: superoxide dismutase 1 (SOD1), profilin 1 (PFN1), S100 calcium-binding protein A11 (S100A11) and kallikrein-related peptidase 6 (KLK6). All four proteins were significantly elevated, with a combined area under the curve of 0.933, while SOD1 alone reached 0.915. Additionally, we observed high glucose and inflammatory conditions reduced SOD1 expression. In conclusion, SOD1 emerges as a promising regulatory target for managing diabetes and periodontitis by modulating the oral oxidative stress microenvironment.