Objective To systematically review literature assessing efficacy and safety of pharmacologic treatments in children with abdominal pain-related functional gastrointestinal disorders (AP-FGIDs). Study design MEDLINE and Cochrane Database were searched for systematic reviews and randomized controlled trials investigating efficacy and safety of pharmacologic agents in children aged 4-18 years with AP-FGIDs. Quality of evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation approach. Results We included 6 studies with 275 children (aged 4.5-18 years) evaluating antispasmodic, antidepressant, antireflux, antihistaminic, and laxative agents. Overall quality of evidence was very low. Compared with placebo, some evidence was found for peppermint oil in improving symptoms (OR 3.3 (95% CI 0.9-12.0) and for cyproheptadine in reducing pain frequency (relative risk [RR] 2.43, 95% CI 1.17-5.04) and pain intensity (RR 3.03, 95% CI 1.29-7.11). Compared with placebo, amitriptyline showed 15% improvement in overall quality of life score (P =.007) and famotidine only provides benefit in global symptom improvement (OR 11.0; 95% CI 1.6-75.5; P =.02). Polyethylene glycol with tegaserod significantly decreased pain intensity compared with polyethylene glycol only (RR 3.60, 95% CI 1.54-8.40). No serious adverse effects were reported. No studies were found concerning antidiarrheal agents, antibiotics, pain medication, anti-emetics, or antimigraine agents. Conclusions Because of the lack of high-quality, placebo-controlled trials of pharmacologic treatment for pediatric AP-FGIDs, there is no evidence to support routine use of any pharmacologic therapy. Peppermint oil, cyproheptadine, and famotidine might be potential interventions, but well-designed randomized controlled trials are needed.