Aim: This study aimed to determine the feasibility and first efficacy of indocyanine green (ICG)-assisted antimicrobial photodynamictherapy (aPDT) as activated using LED light to the dental plaque. Methods: Fifteen healthy adults were assigned to this four-day randomized study. After rinsing with ICG, 100 J/cm2 of 810 nm LED light was applied to the aPDT-treatment area. Plaque area and gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) were measured, and plaque bacteriomes before and after the study were analyzed using 16S rRNA sequencing. Results: aPDT administration was preformed successfully and plaque-specifically with the combination of ICG and the applicator. Total plaque area and endpoint MMP-8 levels were reduced on the aPDT-treatment side. aPDT reduced Streptococcus, Acinetobacteria, Capnocytophaga, and Rothia bacteria species in plaques. Conclusion: ICG-assisted aPDT reduces plaque forming bacteria and exerts anti-inflammatory and anti-proteolytic effects.