Introduction: To systematically review the literature regarding the side effects of pharmacotherapy in children with irritable bowel syndrome (IBS) and functional abdominal pain–not otherwise specified (FAP-NOS). Areas covered: Cochrane Library, PubMed, and Embase databases were searched from inception to May 2018. The following inclusion criteria were applied: (1) randomized controlled trials (RCTs), cohort studies or case-control studies; (2) in children aged 4–18 years or adult studies if children are reported separately; (3) reporting a diagnosis of IBS or FAP-NOS as defined by the authors; and (4) reporting the occurrence of side effects of pharmacotherapy. Quality assessment of included studies was conducted. Expert opinion: A total of 4619 articles were identified; 17 were included. In 10/17 (59%) studies, side effects of pharmacotherapy (antispasmodics, antidepressants, antihistaminic agents, serotonergic agents and antibiotics) occurred. The majority of side effects were: (1) limited to the gastrointestinal tract and central nervous system and, 2) mild and transient. No serious adverse events were reported. This systematic review shows that data on safety in children with functional abdominal pain disorders are scarce, and highlights the lack of high-quality research for potential side effects of pediatric IBS and FAP-NOS. Further research by means of large well-designed-follow-up studies is necessary.