<p>Periodontitis leads to tooth loss, affecting human oral health. The role of microRNA (miRNA) in periodontitis has received increasing attention. This study aims to explore the role of miR-4485-5p in the progression of periodontitis. Baseline clinical data were collected from 93 periodontitis participants and 85 periodontally healthy subjects. The diagnostic value of miR-4485-5p and its correlation with severity were evaluated by the ROC curve and Pearson regression. miR-4485-5p and target gene expression were detected by RT-qPCR and Western blot. The periodontitis cell model was constructed by treating hPDLSCs with P. gingivalis LPS. Cell viability and inflammatory factor levels were detected by CCK-8 and ELISA. The target genes of miR-4485-5p were identified by databases and verified by dual-luciferase reporter assay. miR-4485-5p is downregulated in the saliva of patients with periodontitis. miR-4485-5p effectively distinguishes periodontitis and is negatively correlated with plaque index (PI), bleeding index (BI), probing depth (PD), and clinical attachment level (CAL). LPS inhibits the expression of miR-4485-5p in hPDLSCs, suppresses cell proliferation, and promotes the release of TNF-α, IL-1β, IL-6, and IL-8. Overexpression of miR-4485-5p promotes cell proliferation and inhibits the secretion of inflammatory factors in LPS-induced hPDLSCs. As a target of miR-4485-5p, CDK9 reversed the effects of miR-4485-5p on cell proliferation and inflammatory factors. miR-4485-5p could be the diagnostic biomarker of periodontitis and is correlated with the severity of periodontitis. Overexpression of miR-4485-5p could reverse the cell viability and inflammation in LPS-induced hPDLSCs. While CDK9 could eliminate the effect of miR-4485-5p.</p>