Research has extensively explored the influence of Periodontitis on Alzheimer’s disease (AD), identifying its role in accelerating the disease via systemic inflammation and bacterial invasion to the brain. Additionally, investigations into titanium oxide nanoparticles (Ti NP) and AD have shown significant effects on cognitive ability in vitro and in vivo. This study aims to assess the synergistic impact of Ti NP and P. gingivalis (Pg), factors involved in periimplantitis pathogenesis, on the neuroinflammatory response of mouse microglia cells (BV2) in vitro.Using a BV2 and RAW (separate control) cell culture model, the study tested different concentrations of Ti NP and Pg on inflammatory responses. Eight test groups were established, including control cells, Pg-infected cells, cells exposed to varying Ti NP concentrations, and combinations of Pg infection with Ti NP exposure. After exposure, cell culture supernatants were analyzed for proinflammatory cytokines IL-6, TNF-α, and IL-1β using ELISA, and cell viability was assessed with an XTT test.Results revealed that increasing Ti NP concentrations led to higher secretion of TNF-α and IL-1β by BV2 and RAW cells after 5h and 24h, peaking at 500pg/ml in the group exposed to 100μg/ml of Ti NP. However, cell viability remained unaffected by bacterial infection or Ti NP at the tested conditions. The study suggests a synergistic effect between Pg and Ti NP on the inflammatory response of BBB microglia in vitro, indicating the need for further investigation using more complex co-culture and in vivo models to explore the potential connection between periimplantitis and AD.