OBJECTIVE: To compare the clinical/radiographic outcomes and the rate of disease resolution of the adjunctive use of electrolysis (GS) or hydrogen peroxide (HP) for mechanical decontamination in the reconstructive treatment of peri-implantitis-related intrabony defects. MATERIAL AND METHODS: A multicenter randomized clinical trial was designed to compare the effectiveness and safety of two strategies for the surface decontamination of crater-like and circumferential intrabony defects subjected to reconstructive therapy. Clinical evaluation was made at baseline (T), 6 months (T) and 12 months (T), while radiographic assessment was carried out at T and T. Disease resolution was the primary outcome. Supportive therapy was administered following surgical treatment. Simple and multiple generalized estimating equations (GEE) models were applied to compare the outcomes achieved and to explore potential confounders. Post hoc power calculation was performed to validate the statistical power of the findings. RESULTS: Overall, 58 patients completed the study. All the clinical parameters/indices, namely probing pocket depth, modified sulcular bleeding index, suppuration grading index, and width of keratinized mucosa, showed a significant reduction (p < 0.001) from T to T in both tested groups. Mucosal recession increased (p < 0.001) from T to T. Marginal bone level and radiographic defect angle increased (p < 0.001) from T to T. The disease resolution rate was 87.5% for the GS group and 64.5% for the HP group at T (p = 0.08). No major postoperative complications were reported. CONCLUSION: Both tested surface decontamination methods are effective in resolving peri-implantitis, in gaining radiographic marginal bone levels, and in enhancing clinical peri-implant conditions in the surgical reconstructive therapy (NCT05615051).