Guided bone regeneration (GBR) at peri-implantitis-related bone defects involves the placement of bone-filler particles in the intrabony defects and the application of a barrier membrane. The efficacy of different GBR-supported reconstructive measures as well as their potential superiority compared to non-GBR-supported treatment strategies for bone defects at peri-implantitis sites, however, remains unclear. Therefore, this analysis was designed to evaluate the long-term (≥12 months) clinical efficacy of GBR-supported reconstructive surgical therapy for peri-implantitis-related bone defects. In terms of resolving inflammation, the implementation of GBR protocols applying xenogenic bone substitutes yielded a higher reduction of bleeding on probing and probing depth value compared to the GBR protocol applying autogenous bone. Furthermore, for the changes in bleeding on probing and probing depths, GBR approaches using xenogenic bone showed superiority over the non-GBR treatments. Xenogenic bone with or without a barrier membrane was associated with improved radiographic bone levels and less soft tissue recession compared to the use of a GBR protocol implementing autogenous bone. Nonetheless, when interpreting this findings, the limited number of available studies with low to serious risk of bias and the short follow-up periods limited to 12 months should be considered.