Natural products (NPs) are known to possess a wide range of molecular variety and are found in extracts of complex composition providing a huge chemical diversity of secondary metabolites which is of great interest for drug discovery. The aim of this thesis is to develop strategies for the rapid discovery of natural products with antiepileptic activities by combining bioactivity-guided fractionation methods with in vivo zebrafish assays. Firstly a strategy for high throughput screening activity assessment at the microgram scale through bioactivity-guided fractionation combined to zebrafish in vivo assay has been developed and used to investigate the active principles isolated from plants. In order to obtain efficiently pure bioactive compounds at a large scale isolation platform containing a Medium Pressure Liquid Chromatography (MPLC) was developed and optimized to investigate several plants used in traditional medicine with claimed antiepileptic activities for the discovery of an active anticonvulsant compound from natural extracts.