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The therapeutic discretion in cases of peri-implantitis should take into account the limits and advantages of specific therapeutic itineraries tailored according to each clinical case and each individual patient. This type of oral pathology emphasizes the complex classification and diagnostic issues coupled with the need for targeted treatments, in light of the oral peri-implant microbiota changes. This review highlights the current indications for the non-surgical treatment of peri-implantitis, describing the specific therapeutic efficacy of different approaches and discussing the more appropriate application of single non-invasive therapies The non-surgical treatment choice with antiseptics or antibiotics (single or combined, local, or systemic) for short courses should be considered on a case-by-case basis to minimize the incidence of side effects and concomitantly avoid disease progression.