Objectives This study used a dog model to evaluate two antimicrobial protocols with or without guided bone regeneration (GBR) in the surgical reconstruction of peri‐implantitis defects. Material and methods Eight beagle dogs subject to ligature‐induced peri‐implantitis were used. The animals either received antimicrobial photodynamic therapy or topical tetracycline hydrochloride combined with GBR or as stand‐alone surgical interventions. Block biopsies of the defect sites for histological analysis were obtained at euthanasia, 12 weeks postsurgery. The primary outcome of the study was re‐osseointegration; secondary outcomes included alveolar bone gain and remaining defect characteristics. The effects of the implant site, early exposure, and type of antimicrobial protocol on bone regeneration were also evaluated. Results No significant differences were observed between the two antimicrobial protocols, and the adjunctive use of GBR failed to significantly improve re‐osseointegration or bone gain using either protocol. Buccal sites and implant early exposure negatively affected bone regeneration. Conclusion Both antimicrobial therapies stand‐alone or combined with GBR allowed similar and limited bone gain.