Bacterial biofilms are considered the primary etiology of peri-implant disease. Physical cleaning is the most common way to remove bacterial biofilm, but it can cause grooving, melting, and deposition of chemicals that alter the surface of implants, which may hamper biocompatibility and re-osseointegration. Chemical decontamination is one of the most promising treatments but is limited by low efficiency and poor biocompatibility. Our study aims to develop safer, more effective chemical decontaminants for peri-implant disease prevention and treatment. We focus on resveratrol and naringin, two natural compounds, which have shown to be more effective in decontaminating biofilms on dental implant surfaces and exerting better biocompatibility. This research is groundbreaking as it is the first exploration of natural plant extracts' impact on mature bacterial biofilms on rough titanium surfaces. By advancing this knowledge, we seek to contribute to more effective and biocompatible strategies for combating peri-implant diseases, enhancing oral health, and prolonging implant lifespan.