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<i>Porphyromonas gingivalis</i> is crucial for the pathogenesis of periodontitis. This research investigated the effects of the fruit-derived flavonoid phloretin and its analogs on the growth of pure <i>P. gingivalis</i> and the flora of <i>P. gingivalis</i> mixed with the symbiotic oral pathogens <i>Fusobacterium nucleatum</i> and <i>Streptococcus mitis</i>. The results showed that the tested flavonoids had little effect on the biofilm amount of pure <i>P. gingivalis</i>, but significantly reduced the biofilm amount of mixed flora to 83.6~89.1%. Biofilm viability decreased to 86.7~92.8% in both the pure- and mixed-bacterial groups after naringenin and phloretin treatments. SEM showed that phloretin and phlorizin displayed a similar and remarkable destructive effect on <i>P. gingivalis</i> and the mixed biofilms. Transcriptome analysis confirmed that biofilm formation was inhibited by these flavonoids, and phloretin significantly regulated the transcription of quorum sensing. Phlorizin and phloretin reduced AI-2 activity to 45.9% and 55.4%, respectively, independent of the regulation of related gene transcription. This research marks the first finding that these flavonoids possess anti-biofilm properties against <i>P. gingivalis</i> and its intricate bacterial community, and the observed performance variations, driven by structural differences, underscore the existence of intriguing structure–activity relationships.