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Background: Monochoria hastate (L.) Solms. is extensively used as traditional medicine despite the fact that no scientific data has yet been published revealing its biological activity in vivo. Objectives: The objective of the study was to investigate the pharmacological effect of crude leaf extracts of M. hastate in mice model, justifying its medicinal use and evaluating its safety and efficacy as a crude drug. Materials and Methods: Crude extracts were prepared using methanol and ethyl acetate as solvent. Analgesic activity was evaluated by writhing and formalin-induced licking bioassay. Anti-inflammatory activity was examined by detecting its effect on carrageenan-induced edema. Effect on the central nervous system (CNS) was tested by monitoring movements of test animals by open-field and hole-cross assay. Results: Oral administration (400 mg/kg) of methanol and ethyl acetate extract resulted in 93% and 92% reduction of writhing (P < 0.001) compared to the 87% by diclofenac, whereas ethyl acetate extract caused maximum inhibition (91%) of licking response. Both the extracts manifested marked (P < 0.05) reduction in edema diameter, but the effects were less significant than the standard. Open-field and hole-cross test demonstrated significant (P < 0.001) suppression of motor activity in the treated group. The resulting movements 120 min after oral administration of methanol and ethyl acetate extract (400 mg/kg) and diazepam (1 mg/kg) were 205.8 ± 33, 1.4 ± 0.5, 217 ± 28, 1.0 ± 0.3, 191.2 ± 25, and 2.0 ± 0.7, respectively. Conclusion: These findings provide substantial evidence that leaf extracts of M. hastate possess analgesic, anti-inflammatory, and CNS depressant activity in mice explaining some of its use in traditional medicine.