To evaluate the effect of resveratrol on periodontal bone regeneration after local delivery and to determine its effect on inflammatory mediators. Resveratrol is considered an anti-inflammatory polyphenolic stilbene involved in the modulation of inflammation. Periodontitis was induced in mouse molars using a 5-day ligature model followed by the left second molar extraction and 50µM resveratrol treatment for 1 and 2weeks. We then examined specimens treated for 1week histologically and with immunostaining. Microfocus-computed tomography (micro-CT) was used to examine the bone volume formation. After 1week of treatment, proinflammatory cytokine levels (TNF-alpha and IL6), cells exhibiting neutrophil and macrophage marker (MPO), cell proliferation marker (Ki67), and preosteoblastic marker (RUNX2) reactivity decreased in the resveratrol-treated specimens compared to the control group. In contrast, we observed a higher number of CD31-, F4/80-, and osteocalcin- (OCN-) positive cells in the resveratrol-treated specimens. After 2weeks, micro-CT confirmed an increased bone mass in the region of the extraction socket in the resveratrol-treated group. After 1week, the resveratrol-treated specimens revealed evidence of inflammation modulation compared to the control group. These data suggest that resveratrol not only affects inflammation control but also is useful for treating periodontitis-related tissue defects and bone regeneration.