Dental tissue stem cells (DTSCs) are well known for their multipotent capacity and regenerative potential. They also play an important role in the immune response of inflammatory processes derived from caries lesions, periodontitis, and gingivitis. These oral diseases are triggered by toxins known as lipopolysaccharides (LPS) produced by gram-negative bacteria. LPS present molecular patterns associated with pathogens and are recognized by Toll-like receptors (TLRs) in dental stem cells. In this review, we describe the effect of LPS on the biological behavior of DTSCs. We also focus on the molecular sensors, signaling pathways, and emerging players participating in the interaction of DTSCs with lipopolysaccharides. Although the scientific advances generated provide an understanding of the immunomodulatory potential of DTSCs, there are still new reflections to explore with regard to their clinical application in the treatment of oral inflammatory diseases.