Periodontitis is a multifactorial inflammatory disease characterized by persistent inflammation, oxidative imbalance, and impaired regenerative capacity within periodontal tissues. Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) is a key pathogenic factor that disrupts periodontal cell homeostasis. The present study aimed to evaluate the protective effects of CPS-28 against Pg-LPS-induced dysfunction in human periodontal ligament (HPDL) cells.CPS-28 has been reported to have anti-inflammatory, antioxidant, anticancer and antibacterial effects. Due to these properties, CPS-28 has demonstrated pharmacological effects in various diseases, including neurodegenerative diseases, arthritis and cardiovascular diseases. In this study, we investigated the therapeutic effect of CPS-28 on periodontitis using HPDL cells. The results showed that CPS-28 reduced the inflammation and oxidative stress induced by Pg-LPS. Consequently, it increased the expression of antioxidant enzymes such as SOD and CAT, as well as osteogenic related markers including ALP, RUNX2 and OPN, which had been suppressed by Pg-LPS. Collectively, these findings indicate that CPS-28 mitigates Pg-LPS-induced periodontal cell dysfunction by modulating inflammatory responses, reinforcing antioxidant capacity, and preserving osteogenic potential. CPS-28 may therefore represent a promising candidate for the management of periodontitis.