During wound healing, cells situated in the periodontal ligament communicate with each other and induce the healing process. The periodontal ligament stem cells migrate to the inflamed site and differentiate into mesenchymal origin cells in response to chemokines. Various mediators induce the healing process, such as interleukins, PDGF, TGF-b, IGF- 1, FGF-2, VEGF, and EGF. Non-coding RNAs have been found to be associated with inflammatory reactions including periodontal diseases. The important functions of cytokines and the gene expression levels in regulating PDL cells has given researchers more ideas and possibilities to use them as regenerative agents. Biological mediators are potential therapeutic agents for periodontal regeneration.