The aim of this preliminary study is to show the effect of the biofilm decontamination approach on peri-implantitis treatment. Clinical cases showing peri-implantitis were treated using an oral tissue decontaminant material that contains a concentrated aqueous mixture of hydroxybenzenesulfonic and hydroxymethoxybenzenesulfonic acids and sulfuric acid. The material was positioned in the pocket around the implant without anesthesia in nonsurgically treated cases. No instrumentation and no systemic or local antibiotics were used in any of the cases. A questionnaire was used for each patient to record the pain/discomfort felt when the material was administered. All of the treated cases healed well and rapidly. The infections were quickly resolved without complications. The momentary pain on introduction of the material was generally well tolerated and completely disappeared after a few seconds. The biofilm decontamination approach seems to be a very promising technique for the treatment of peri-implantitis. The local application of this material avoids the use of systemic or local antibiotics.