Bone quality is an important issue in dentistry. Low bone density may be associated with more severe periodontitis, and may influence implant therapy success. Recent evidence suggests that physical activity can improve alveolar bone quality. Irisin is an exercise-mediated peptide that might be involved in this process. We assessed the effect of exercise and that of intra-peritoneal irisin administration on bone quality in healthy and osteoporosis-induced rodents. This study was registered at PROSPERO (CRD42020184140), and followed PRISMA guidelines. A search by two independent examiners was conducted in five databases and gray literature up to July 2021, without restrictions regarding language or date of publication. Initially, they analyzed retrieved titles and abstracts (n=3,844) based on eligibility criteria. Of this total, 19 studies remained for full-text reading, and 16 proceeded to the data extraction and quality assessment phases. Meta-analyses were conducted (n= 6 studies) to establish the effects of irisin administration on cancellous bone mineral density (BMD). Exercise or irisin administration enhanced bone quality, but the meta-analysis showed that BMD increased only slightly in osteoporotic rodents (BMD: mean difference 0.03 mg/cm3 - 95% CI 0.01-0.05). This indicates that they had no significant benefits on the bones of healthy animals. Implications of key findings evidence the potential of irisin as an agent able to mitigate bone loss caused by osteoporosis, an outcome that could favor dental rehabilitation. More studies investigating the effect of irisin on alveolar bone are needed to elucidate its therapeutic viability and implications.