Carvacrol and dimeric chalcones are the respective bioactive components of Lippia sidoides and Myracrodruon urundeuva, popular medicinal plants of Northeastern Brazil with proven antimicrobial and antiinflammatory properties. Periodontal disease is associated with inflammation and microbiological proliferation, thus the study aimed to investigate the effect of a topical gel based on carvacrol and chalcones in the experimental periodontal disease (EPD) in rats. Animals were treated with carvacrol and/or chalcones gel, immediately after EPD induction, three times a day for 11 days. Appropriate controls were included in the study. Animals were weighed daily. They were killed on day 11, the mandibles dissected and alveolar bone loss was measured. The periodontium were examined at histopathology and the neutrophil influx into the gingiva was assayed using myeloperoxidase activity. The bacterial flora were assessed through culture of the gingival tissue. Alveolar bone loss was significantly (p < 0.05) inhibited by combined carvacrol and chalcones gel, compared with the vehicle and non-treated groups. The treatment with the combined gel reduced tissue lesion at histopathology, decreased myeloperoxidase activity in gingival tissue and inhibited the growth of oral microorganisms as well as the weight loss. Carvacrol and chalcones combination gel has a beneficial effect upon EPD in this model.