Aim To evaluate the effect of red wine consumption or its polyphenols on the inflammation/resorption processes associated with apical periodontitis in rats. Methodology Thirty‐two three‐month‐old Wistar rats had apical periodontitis induced in four first molars and were then arranged into four groups: control (C)—rats with apical periodontitis; wine (W)—rats with apical periodontitis receiving 4.28 ml/kg of red wine; resveratrol+quercetin (R+Q)—rats with apical periodontitis receiving 4.28 ml/kg of a solution containing 1.00 mg/L of quercetin and 0.86 mg/L of resveratrol and alcohol (ALC)—rats with apical periodontitis receiving the alcoholic dose contained in the wine. The oral gavage treatments were administered daily, from day 0 to day 45. On the 15th day, apical periodontitis was induced, and on the 45th day, the animals were euthanized. Histological, immunohistochemical (RANKL, OPG, TRAP, IL‐10, TNF‐⍺ and IL‐1β) and micro‐computed tomography for bone resorption analysis were performed in the jaws. The Kruskal–Wallis with Dunn's test was performed for nonparametric data, and the anova with Tukey's test for parametric data, p < .05. Results The median score of the inflammatory process was significantly lower in the R+Q group (1) compared to the C (2) (p = .0305) and ALC (3) (p = .0003) groups, and not different from the W (1.5) group. The immunolabeling for OPG was significantly higher in the R+Q group (p = .0054) compared to all groups; the same was observed for IL‐10 (p = .0185), different from groups C and ALC. The R+Q group had the lowest TRAP cell count (p < .0001), followed by the W group, both inferior to C and ALC groups. The lowest bone resorption value was in the R+Q group (0.50mm3 ± 0.21mm3), significantly lower (p = .0292) than the C group (0.88mm3 ± 0.10mm3). The W group (0.60 mm3 ± 0.25 mm3) and R+Q group had less bone resorption compared to the ALC group (0.97 mm3 ± 0.22 mm3), p = .0297 and p = .0042, respectively. Conclusion Red wine administration to rats for 15 days before induction of apical periodontitis decreased inflammation, TRAP marking and periapical bone resorption compared to alcohol. Resveratrol‐quercetin administration reduced the inflammatory process in apical periodontitis, periapical bone resorption, and altered the OPG, IL‐10 and TRAP expression compared to C and ALC groups.