Air-polishing with low abrasiveness powders is fast arising as a valid and mini-invasive instrument for the management of biofilm colonizing dental implants. In general, the reported advantage is the efficient removal of plaque with respect to the titanium integrity. In the present study, we evaluated the in situ plaque removal and the preventive efficacy in forestalling further infection of an innovative erythritol/chlorhexidine air-polishing powder and compared it with sodium bicarbonate. Accordingly, two peri-implantitis-linked biofilm formers, strains Staphylococcus aureus and Aggregatibacter actinomycetemcomitans, were selected and used to infect titanium disks before and after the air-polishing treatment to test its ability in biofilm removal and re-colonization inhibition, respectively. Biofilm cell numbers and viability were assayed by colony-forming unit (CFU) count and metabolic-colorimetric (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) (XTT) assay. Results demonstrated that air-polishing performed with either sodium bicarbonate or erythritol/chlorhexidine was effective in reducing bacteria biofilm viability and number on pre-infected specimens, thus showing a similar ability in counteracting existing infection in situ; on the other hand, when air-polished pre-treated disks were infected, only erythritol/chlorhexidine powder showed higher post-treatment biofilm re-growth inhibition. Finally, surface analysis via mechanical profilometry failed to show an increase in titanium roughness, regardless of the powder selected, thus excluding any possible surface damage due to the use of either sodium bicarbonate or erythritol/chlorhexidine.