Objectives: To determine the anti-inflammatory and antinociceptive activities of Mitragyna speciosa Korth methanol extract in rodents. Materials and Methods: Anti-inflammatory activity was evaluated using carrageenan-induced paw edema and cotton pellet-induced granuloma tests in rats. Antinociceptive activity was measured using the writhing test and the hot plate test in mice, and the formalin test in rats. All drugs and extracts were diluted in dH2O and administered through the intraperitoneal route. Results were analyzed using one-way ANOVA followed by Dunnett’s test for multiple comparisons among groups. Results: Results showed that intraperitoneal administration of the extract at doses of 100 and 200 mg/kg produced significant dose-dependent activity in all of the nociceptive models evaluated (p < 0.05). With the formalin test, the antinociceptive activity in mice was inhibited only at the highest dose of the extract (200 mg/kg). The study also showed that intraperitoneal administration of the methanol extract of M. speciosa (100 and 200 mg/kg) significantly and dose-dependently suppressed the development of carrageenan-induced rat paw edema (p < 0.05). In the chronic test, however, significant reduction in granulomatous tissue formation in rats was observed only at the highest dose of the methanol extract of M. speciosa (200 mg/kg, p < 0.05). Conclusion: The present study suggests the presence of potent antinociceptive and anti-inflammatory principles in the extract, supporting its folkloric use for the treatment of these conditions.