Abstract Background Capparis spinosa L is a Mediterranean plant. In Libya, the plant grows in rocky areas and at high altitudes. It is commonly used by the inhabitants of the Mediterranean region in their kitchen and treatment of many diseases. Aim This study was undertaken to investigate the central nervous system depressant, anticonvulsant, and the muscle relaxant activities of orally administered methanolic extract from the leaves of C. spinosa L. (MECS) in mice. Methods The oral administration of three doses of the MECS in mice (500, 1000, and 2000 mg/kg) were evaluated in the picrotoxin (PC)-induced convulsion model, ketamine-induced sleep, and rota rod test. Diazepam was used as a reference drug for comparison. Results were analyzed using SPSS program version 16. Data are presented as mean ± SEM, and compared using one-way ANOVA followed by Duncan's test. The significance level was set at p < 0.05 Results Oral administration of MECS (1000 and 2000 mg/kg) significantly prolonged the onset of seizures (p < 0.01) and produced dose-dependent protection against PC-induced seizures compared with the control group (12.5% and 50% protection, respectively). MECS significantly (p < 0.05) and dose dependently reduced ketamine sleep latency (from 3.16 ± 0.16 to a minimum of 1.5 ± 0.22 minutes) and prolonged ketamine-induced sleeping time (from 11.33 ± 1.99 to a maximum of 33.33 ± 0.95 minutes). In the accelerated rotarod test, MECS significantly (p < 0.01) decreased the riding time on the rotarod (from 128.83 ± 14.6 to a minimum of 1.83 ± 0.47 seconds) as compared with the normal saline control group. Conclusion The results showed that the MECS possesses anticonvulsant, sedative, and muscle relaxant properties in mice.