Resveratrol reduced COX2, MMP-2, MMP-9, TLR4 expression and the activation of MAPK signaling pathway while activating the NRF2/HO-1 axis, reducing ROS levels. Resveratrol protected a periodontitis rat model against alveolar bone loss, inhibiting inflammation and osteoclast formation and increasing NRF2 and HO-1 expression in the gingiva of rats. This evidence concerns the gene NFE2L2 and periodontitis.