Objective: To evaluate the effect of resveratrol on periodontal bone regeneration after local delivery and to determine its effect on inflammatory mediators. Background: Resveratrol is considered an anti‐inflammatory polyphenolic stilbene involved in the modulation of inflammation. Materials and Methods: Periodontitis was induced in mouse molars using a 5‐day ligature model followed by the left second molar extraction and 50 µM resveratrol treatment for 1 and 2 weeks. We then examined specimens treated for 1 week histologically and with immunostaining. Microfocus‐computed tomography (micro‐CT) was used to examine the bone volume formation. Results: After 1 week 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 2 weeks, micro‐CT confirmed an increased bone mass in the region of the extraction socket in the resveratrol‐treated group. Conclusion: After 1 week, 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.