Periodontitis, a persistent inflammatory condition, targets the gums and periodontal structures, negatively impacting health. Systemic and local antimicrobials are often used to treat periodontitis, but they may lead to adverse effects such as drug resistance and ecological imbalance. As natural water-soluble pigment, anthocyanins have been reported to be an effective antiinflammatory, antiobesity, anticancer, antimicrobial and so on. The purpose of the study was to elucidate the anti-inflammatory effects and potential molecular mechanisms of purple red rice bran anthocyanins (PRBA) on RAW264.7 cells induced by lipopolysaccharide from Porphyromonas gingivalis (Pg-LPS). The results indicated that PRBA inhibited the expression of iNOS and COX-2 in RAW264.7 cells, reduced the level of NO, TNF-α, and IL-6, while increasing the expression of Arg-1 and the production of IL-10 in RAW264.7 cells. Among them, cyanidin-3-glucoside and peonidin-3-glucoside, the 2 main anthocyanin glycosides in PRBA, also had the same effects. RNA-seq results revealed that there were 1840 differentially expressed genes (DEGs) after PRBA treatment, with 1263 upregulated and 577 downregulated. Western blot also confirmed that PRBA significantly inhibited the activation of NF-κB and AP-1 in RAW264.7 cells. In summary, these findings suggested that PRBA inhibited the expression of proinflammatory cytokines in RAW264.7 cells induced by Pg-LPS through the NF-κB and AP-1 pathways, which providing its potential application in the treatment of periodontitis for anti-inflammatory effects.