Currently, the best available treatment is symptomatic management, there is no complete cure for Peutz-Jeghers syndrome itself, so management focuses on removing polyps before they cause complications, catching cancers at their earliest and most treatable stage, and coordinating care across the many organ systems that can be affected. Care is generally best delivered by a team that includes a gastroenterologist, a geneticist or genetic counsellor, and, depending on findings, specialists in gynaecology, endocrinology, and oncology.

• Endoscopic polyp removal, called polypectomy, is the main treatment for polyps once they reach about one centimetre in size. Removing polyps at this stage reduces the risk of bleeding, obstruction, and intussusception, and may also lower the long-term cancer risk associated with these polyps.
• Small-bowel imaging and treatment techniques have advanced considerably in recent years. Video capsule endoscopy, in which a small-swallowed camera captures images as it passes through the digestive tract, is now generally preferred as the first-line method for detecting small-bowel polyps, with magnetic resonance enterorrhaphy as a reliable alternative that avoids radiation exposure. Balloon-assisted enteroscopy allows many polyps deep in the small bowel to be removed without open surgery, reserving surgical removal of bowel tissue for polyps that cannot be reached this way.
• Intussusception and malignancies, when they occur, are treated using standard surgical and oncologic approaches.
• Hormonal tumours, such as oestrogen-producing testicular tumours in boys, can sometimes be managed with medications called aromatase inhibitors, which can reduce breast tissue growth and slow accelerated bone growth if treatment is started before puberty is complete.
• Preventive surgery, such as removal of the breasts, ovaries, or uterus, is not yet supported by strong evidence specific to Peutz-Jeghers syndrome but may be considered on an individual basis in discussion with a specialist centre, taking family history and personal risk factors into account.

Because tobacco use appears to further increase the already elevated risk of certain cancers, including of the cervix, lung, and pancreas, smoking avoidance and cessation support are an important part of care. Research into medications that might reduce polyp formation, including certain anti-inflammatory drugs and cell-growth pathway inhibitors, is ongoing, though none has yet been established as a standard therapy.