Many studies have documented the important role of the gut microbiota (GM) in the regulation of several central nervous system (CNS) processes through the microbiota-gut-brain (MGB) axis. This latter represents the connection between the CNS, the enteric nervous system, the gut and its microbiota through several ascending and descending pathways. The variation of the GM composition is associated with the pathogenesis and/or progression as well as severity of various neuropsychiatric/neurological diseases such as depression, autism spectrum disorder, multiple sclerosis, Parkinson's, and Alzheimer's diseases. Recently, changes in the bacterial composition of the GM have also been linked to epilepsy and seizures, with some studies exploring the potential role of GM in the regulation of neuronal hyperexcitability, seizure occurrence and epileptogenesis. Accordingly, there are potential novel treatments which are currently being investigated such as probiotics, prebiotics and symbiotic that may represent innovative therapeutic approaches. The aim of this review is to explore the effect of gut microbiota manipulation as a therapeutic strategy in epilepsy and the methodological challenges to design (translational) clinical trial investigating the gut microbiota.