Abstract The aim of this study was to evaluate the effects of adjunct systemic antibiotic treatment with metronidazole (MTZ) and amoxicillin (AMX) in patients receiving non-surgical subgingival debridement (NSD) for peri-implantitis. Forty subjects presenting with at least one implant with severe peri-implantitis were randomized into an experimental group [treated with NSD plus MTZ (400 mg) and AMX (500 mg) three times a day for 14 days] and a control group treated with NSD plus placebo. Clinical parameters and submucosal biofilm profiles were evaluated up to 1 year post-treatment. Overall, both treatments improved clinical parameters over time. At 1 year, mean probing depth (PD), mean clinical attachment (CA) level and proportions of red complex pathogens did not differ significantly between the two groups. In addition, mean PD and CA changes to 1-year posttreatment did not differ significantly between the two groups between baseline and 1-year post-treatment. These results suggest that the addition of MTZ and AMX to the treatment protocol of patients undergoing NSD for with severe peri-implantitis does not improve the clinical and microbiological outcomes of NSD. The fact that half of the implants in both groups did not achieve clinical success (PD < 5 mm, no BoP, no bone loss) suggest that neither of the tested protocols were effective for treating severe peri-implantitis.