Recently, the existence of the tissue renin-angiotensin system (tRAS) has been described for multiple tissues in humans, suggesting its fundamental role in the progression of inflammation and fibrosis. Evidence arises that tRAS might have an impact on the progression of periodontitis and bone loss. However, neither the role of tRAS nor its impact as a therapeutic target have been systematically evaluated for periodontal tissue. The present study sought to characterise tRAS in the periodontal tissue and the effect of its inhibition on periodontal inflammation and bone loss. This systematic review was performed according to the preferred reporting items for systematic reviews and meta analyses (PRISMA) statement. Literature was searched using Web of Science core collection (Web of Science), Medline (Ovid), Cochrane central register of controlled trials (Ovid), Cochrane database of systematic reviews (Ovid), Google Scholar databases and the references of the retrieved studies in March 2020. Information on study design, sample size, population, procedure, type of intervention, observation time, as well as information on sources of bias, was extracted and evaluated. From 455 identified articles, 17 were included in the qualitative synthesis and 11 were included in the quantitative synthesis. Outcomes of studies indicated that the inhibition of tRAS components led to a reduction of periodontal bone loss and inflammation, dependent on the inhibitor used. The findings suggested an important role of tRAS in the periodontal tissue and indicate a potential therapeutic approach for periodontal diseases.