Prucalopride is a third-generation, highly selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist. Many recent studies indicate prucalopride may play an important role in various motility disorders. The aim of this study was to investigate safety and patient selection considerations when using prucalopride as gastroparesis and chronic constipation treatment. We systematically searched PubMed, Embase, the Cochrane Central Register and ClinicalTrials.gov, and we reviewed all studies that evaluated prucalopride for the treatment of gastroparesis and chronic idiopathic constipation in adults. Prucalopride is an effective and safe option based on all the studies currently conducted. Thus, it may be the first-line treatment in the future. Prucalopride has the potential to be useful in the treatment of functional constipation and other forms of gastrointestinal diseases (eg, gastroparesis). Through the research on this potential, prucalopride is expected to be a useful and versatile option for treating gastrointestinal diseases in the future.