Peri-implantitis is an increasingly prevalent condition that, if left untreated, can lead to implant failure and loss. Numerous regenerative treatment modalities have been reported in the literature with varying degrees of success. Unfortunately, there is little consensus regarding optimal methods for predictable regeneration of the peri-implant bone lost due to the disease. This case report presents a 68-year-old healthy, nonsmoking man with peri-implantitis affecting the endosseous implant that replaced the maxillary left first molar. After unsuccessful nonsurgical debridement, regenerative surgical therapy was recommended. Guided bone regeneration (GBR) was performed using natural bovine bone mineral covered with a dehydrated human deepithelialized human amnion-chorion membrane (ddACM). Implant surface decontamination was achieved using a titanium brush. Posttreatment clinical assessment suggested that the patient responded well to surgical regenerative therapy. This response was characterized by the reestablishment of healthy peri-implant soft tissues. From a radiographic perspective, complete bone fill of the peri-implant bony defect was seen. These outcomes were maintained over 2 years. This case demonstrates that it is possible to treat peri-implantitis successfully and obtain stable long-term results with a GBR approach utilizing a xenogeneic bone substitute with ddACM.