Origanum majorana L. widely used in Jordan and other Mediterranean countries as a flavoring and herbal spice. An infusion of the plant is used for treatment of internal diseases, haemorrhoids, pains, and animal bites and poisons. In this study, we attempted to identify the possible antinociceptive action of Origanum majorana methanol leaf extract using tail immersion, hot plate, and writhing tests. The antinociceptive effect of the methanol extract of Origanum majorana (MEO) leaves was assessed after intraperitoneal administration into mice. Morphine sulfate (5 mg/kg; i.p.) and diclofenac (10 mg/kg; i.p.) were used as reference analgesic agents. Naloxone (5 mg/kg; i.p.) was also tested. MEO was studied at the doses of 50, 100, and 200 mg/kg (i.p.) and exhibited significant antinociceptive activities in all tests used. The above-mentioned doses of the extract reduced the writhing responses by 24.51, 52.11, and 72.43%, respectively. MPE% was increased by 10.51, 15.07, 22.40% in the tail immersion, and 12.38, 14.31, 22.14 % in the hot plate test at the tested doses, respectively. Naloxone antagonized antinociceptive effect at the doses of 100 and 200 mg/kg whereas partially antagonized the effect of MEO at the dose of 50 mg/kg. Based on the results obtained, it can be concluded that MEO has antinociceptive effects both at the peripheral and central levels.