Abstract Objectives Numerous studies have shown the pharmacological effects of pomegranate, such as: anti-cancer, cholesterol-lowering, anti-diabetic, and antihypertensive features. Pomegranate consumption has also revealed some adverse effects. This systematic review aimed to explore the adverse effects of pomegranate reported in clinical studies. Content The keywords “pomegranate”, “Punica granatum”, “side effect”, “clinical trial”, and “case report or case series” were searched for in valid databases. Reports about adverse effects of pomegranate were also collected from several international registries. Summary This systematic review included a total of 66 clinical articles. Eleven articles have reported side effects of pomegranate. Twenty-one articles have recorded no side effects in the pomegranate group while 34 articles have not mentioned any side effects for this plant. The study also included 7 case report studies. The most common side effects included gastrointestinal problems, flu-like symptoms, and urinary problems. In case report studies, the most significant reported side effect was allergic reaction. Outlook In summary, pomegranate and its extract seem to be safe according to the reported adverse effects. Meanwhile, conducting more robust controlled trials with pomegranate products and documentation of any probable side effect is warranted.