Hyptis pectinata L. Poit, known as ‘sambacaitá’, is used in Brazil to treat inflammatory and painful disorders. In this study, the antioxidant and orofacial antinociceptive properties of the aqueous extract of H. pectinata leaves (AEPH) were assessed using in vitro and in vivo models. Thus, AEPH reduced the 2,2-diphenyl-1-picrylhydrazyl radical up to 72.10% with an EC50 of 14.56 µg/ml. It also inhibited 40.80% of the lipoperoxidation induced by 2′-azobis (2-amidinopropane) dihydrochloride in the thiobarbituric acid-reactive substances assay. The orofacial antinociceptive activity was evaluated in mice pre-treated with AEPH (100, 200 and 400 mg/kg, p.o.) and morphine (5 mg/kg, i.p.), which received afterwards formalin- (20 µl, 2% solution, s.c.), glutamate- (40 µl, 25 mM, s.c.) and capsaicin- (20 µl, 2.5 µg, s.c.) to induce orofacial nociception. AEPH at all doses reduced (p < 0.001) the nociceptive response in the first (43–62%) and second (47–80%) phases of the formalin test. Besides, the effect of AEPH (400 mg/kg) was not changed in the presence of naloxone (1.5 mg/kg, i.p.), an opioid antagonist. AEPH significantly inhibited mice face rubbing for capsaicin (23–69%, p < 0.05) and glutamate (48–77%, p < 0.001) at all doses. The findings suggested the AEPH has peripheral and central antinociceptive activities, which are not related to opioid receptors. Copyright © 2012 John Wiley & Sons, Ltd.