<p>Peri-implantitis (PI) is a prevalent complication of denture implantation, and the consequences of PI on dental implantation are irreversible. This research examined the levels and clinical significance of miR-486-5p in PI patients, while also investigating its biological role in the PI progression using a cellular model. Quantitative polymerase chain reaction (qPCR) was employed to assess the miR-486-5p levels. The diagnostic significance of miR-486-5p, along with its relationship to periodontal indicators and prognosis, was evaluated through ROC and Pearson correlation analysis. Additionally, the LPS cell injury model was established to investigate the effects of both the miR-486-5p overexpression and inhibition on the proliferation and apoptosis of hPDLFs utilizing CCK-8 and flow cytometry. Furthermore, the miR-486-5p regulation on inflammatory factors and oxidative stress levels was assessed through ELISA. The miR-486-5p levels in PI patients were elevated, demonstrating considerable diagnostic potential for this condition. miR-486-5p might serve as an important indicator for assessing the periodontal status and prognosis of PI patients. In cell models, miR-486-5p overexpression could inhibit proliferation and promote apoptosis of hPDLFs, as well as enhance the inflammatory mediators release and oxidative stress-related damage. Conversely, the inhibition of miR-486-5p expression could counteract the promoting effect of LPS on inflammatory response. miR-486-5p is a potential diagnostic biomarker of PI. The up-regulated miR-486-5p might intensify inflammatory responses and impair cellular functionality, consequently facilitating the progression of PI.</p>