Periodontitis is a chronic inflammatory disease induced by bacteria from oral biofilms. Bacteria interact with host cells and can subsequently provoke activation of polymorphonuclear neutrophils (PMNs). In this study, an in vitro model was applied to investigate interactions between periodontal pathogens, i.e., P. intermedia, T. forsythia and P. gingivalis, human dental stem cells (hDFSCs) and PMNs. HDFSCs modulate immune activity of PMNs after infection with oral bacteria implying general suitability of hDFSCs in tissue regeneration strategies after tissue damage in periodontal infections.