Background and Purpose: A relationship between gut microbiome and central nervous system (CNS), have been suggested. The human microbiome may have an influence on brain's development, thus implying that dysbiosis may contribute in the etiology and progression of some neurological/neuropsychiatric disorders. The objective of this systematic review was to identify evidence on the characterization and potential distinctive traits of the microbiome of children with neurodevelopmental disorders, as compared to healthy children. Methods: The review was performed following the methodology described in the Cochrane handbook for systematic reviews, and was reported based on the PRISMA statement for reporting systematic reviews and meta-analyses. All literature published up to April 2019 was retrieved searching the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. Only observational studies, published in English and reporting data on the characterization of the microbiome in humans aged 0-18 years with a neurodevelopmental disorder were included. Neurodevelopmental disorders were categorized according to the definition included in the Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5). Results: Bibliographic searches yielded 9,237 records. One study was identified through other data sources. A total of 16 studies were selected based on their relevance and pertinence to the topic of the review, and were then applied the predefined inclusion and exclusion criteria. A total of 10 case-control studies met the inclusion criteria, and were thus included in the qualitative analysis and applied the NOS score. Two studies reported data on the gut microbiome of children with ADHD, while 8 reported data on either the gut (n = 6) or the oral microbiome (n = 2) of children with ASD. Conclusions: All the 10 studies included in this review showed a high heterogeneity in terms of sample size, gender, clinical issues, and type of controls. This high heterogeneity, along with the small sample size of the included studies, strongly limited the external validity of results. The quality assessment performed using the NOS score showed an overall low to moderate methodological quality of the included studies. To better clarify the potential role of microbiome in patients with neurodevelopmental disorders, further high-quality observational (specifically cohort) studies are needed.