Current regenerative strategies for alveolar bone and periodontal tissues are effective and well adopted. These are mainly based on the use of a combination of synthetic/natural scaffolds and bioactive agents, obviating the incorporation of cells. However, there are some inherent limitations associated with traditional techniques, and we hypothesized that the use of cell-based therapies as part of comprehensive regenerative protocols may help overcome these hurdles to enhance clinical outcomes. We conducted a systematic review of human controlled clinical trials investigating the clinical and/or histological effect of the use of cellbased therapies for alveolar bone and periodontal regeneration and explored the translational potential of the different cell-based strategies identified in the included trials. A total of 16 studies (11 randomized controlled trials, 5 controlled clinical trials) were included for data synthesis and qualitative analysis with meta-analyses performed when appropriate. The results suggest a clinical benefit from the use of cell therapy. Improved outcomes were shown for alveolar ridge preservation, lateral ridge augmentation, and periodontal regeneration. However, there was insufficient evidence to identify best-performing treatment modalities amongst the different cell-based techniques. In light of the clinical and histological outcomes, we identify extraction socket and challenging lateral and vertical bone defects requiring bone block grafts as strong candidates for the adjuvant application of mesenchymal stem cells. Given the complexity, invasiveness, and costs associated with techniques that include "substantial manipulation" of tissues and cells, their additional clinical benefit when compared with "minimal manipulation" must be elucidated in future trials. STEM CELLS Cell-based therapies have the potential to improve outcomes of regenerative treatment in the oral cavity. Extraction sockets and challenging lateral/vertical bone defects requiring bone block grafts are ideal candidates for the adjuvant application of mesenchymal stem cells. The present review showed that there is insufficient evidence to identify best-performing treatment modalities among the different cell-based techniques. Given the complexity, invasiveness, and costs associated with the "substantial manipulation" of tissues and cells, the clinical benefit of these techniques when compared with "minimal manipulation" must be elucidated. Further research evaluating the effectiveness of simple, fast, and economical methods for cell harvesting and processing is warranted.