In this study, an inclusion complex with beta-cyclodextrin and farnesol (beta CD/FAR) was used to improve the physico-chemical and pharmacological properties of famesol. The samples were obtained using the physical mixture, paste and slurry complexation methods and characterized by variety of methods. To evaluate the pharmacological effect, an animal model of orofacial pain induced by formalin, glutamate and capsaicin was used, and its possible mechanisms of action were evaluated. The slurry complexation method was produced with a formation energy of 3.45 kcal/mol and exhibited a better complexation profile as it presented smaller, deformed crystals compared to the other methods, with a stable complex formed. The formation energy was 3.45 kcal/mol. In the orofacial pain test induced by formalin, capsaicin and glutamate the results show that farnesol and its complex at doses of 50 and 100 mg/kg significantly decreased (p < 0.001) face-rubbing behavior. In the investigation of the mechanism of action, the administration of glibenclamide and ondansetron modified the antinociceptive effect of the famesol, suggesting the possible participation of the ATP-sensitive K+ channel (K-ATp(+)) and 5-hydroxytryptamine (5-HT3) channels/receptors. A rota-rod test did not show any significant alterations in motor performance in the groups treated with farnesol and its complex. In conclusion, famesol and beta CD/FAR reduced orofacial pain, possibly mediated by Kjtrp channels and 5-HT3 receptors.