To evaluate the use of guided bone regeneration with xenograft to prevent periodontal defect in the distal aspect of the second molar after the surgical removal of the mandibular third molar. Three electronic databases (Pubmed, Cochrane Library and Scopus) were searched in April 2020. Randomized clinical trials in non-smokers and healthy patients, with at least six months follow-up, comparing periodontal probing depth, clinical attachment level, alveolar bone level and adverse events were selected by two independent investigators. The risk of bias assessment of the selected studies was evaluated by means of the Cochrane Collaboration?s Tool. Finally, a meta-analysis of the outcomes of interest was performed. Despite 795 articles were found in the initial search, only three randomized controlled clinical trials were included. Pooled results favoured the use of the xenograft plus collagen membrane over the spontaneous healing in terms of periodontal probing depth gain (MD=2.36; 95% CI 0.69 to 4.03; P=0.005) and clinical attachment level gain (MD=2.52; 95% CI 0.96 to 4.09; P=0.002). No other statistically significant differences were found. Within the limitations of the present review, the xenograft plus collagen membrane exhibited better periodontal results than spontaneous healing without increasing postoperative complications. However, future well-designed studies with larger samples are required to confirm our results.