Pain is a normal response of the central nervous system to trauma, infections, neoplasms, neuropathies, and inflammation. It can arise from physical, emotional, or cognitive conditions, and is classified as orofacial pain when it affects the mouth and face. Umbelliferone, a coumarin from the umbelliferous plant family, is an important component of essential oils, and possesses antioxidant, curative, anti-inflammatory, and anti-tumor activity. The aim of this study was to investigate the orofacial antinociceptive and anti-inflammatory effects of umbelliferone in Swiss male mice Mus musculus, at 3 months of age. Test groups received different doses of umbelliferone (25, 50, or 75 mg/kg, i.p.). The negative control received 0.9% sodium chloride and Tween 80, with the positive control receiving morphine (5 mg/kg, i.p.) or dexamethasone (2 mg/kg, s.c.). We observed a significant reduction in acetic acid-induced abdominal writhing (p<
0.001), and a decrease in paw licking in the orofacial nociception test with formalin (p <
0.01). The 50 and 75 mg/kg doses of umbelliferone presented significant reductions in the glutamate (p<
0.01) and capsaicin (p<
0.01) tests, suggesting activity on glutamatergic receptors and TRPV1. In the carrageenan-induced paw edema test (1%), there was a decrease in limb volume over 240 minutes (p<
0.01), suggesting inhibition of the inflammatory process. There was also a reduction in leukocyte count (p<
0.001) and TNF-α levels (p<
0.001) when compared to the control group, being similar to the animals treated with dexamethasone (p<
0.001). It was concluded that umbelliferone exhibits orofacial antinociceptive activity and anti-inflammatory activity via TNF-α. However, further preclinical studies are needed for a better characterization.