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Porphyromonas gingivalis causes various health issues through oral infections. This study investigates the antibacterial activities of food-derived dihydrochalcone flavonoids against Porphyromonas gingivalis and their mechanisms of antibacterial action through comparative transcriptome profiling. Susceptibility tests showed that two typical dihydrochalcone flavonoids (phloretin and phlorizin) had much lower minimum inhibitory concentrations (12.5 μg mL -1 and 50 μg mL -1 , respectively) than the common flavanone naringenin (100 μg mL -1 ). SEM observations and the LDH activity assay indicated obvious anomalies in cell morphology and increased cell membrane permeability, indicating the destructive effect of those compounds on the cell structure. These compounds might also induce apoptosis in P. gingivalis , as shown by the CLSM fluorescence images. Transcriptomic analysis revealed that the flavonoid treatment impacted DNA function and oxidative damage. These flavonoids may activate antioxidant-related pathways that are lethal to anaerobic bacteria like P. gingivalis . Additionally, the compounds resulted in the silencing of transposition-related genes, potentially inhibiting resistance-gene acquisition and expression. Phloretin regulated fatty acid metabolism pathways, which are related to the construction and maintenance of the cell membrane. This suggests a relationship between the structure and antibacterial activities of the tested compounds that share a flavonoid skeleton but differ in the C-ring and glucose moiety. This is the first report of the antibacterial activities and mechanisms of action of food-derived dihydrochalcone flavonoids at the transcriptome level, offering a promising approach for the development of new antibacterial agents from natural products and enhancing their applicability in treating diseases associated with oral pathogens as a substitute for antibiotics.