Objective To investigate the medication advancement of gastrointestinal polyposis in patients with Peutz-Jeghers syndrome (PJS). Methods Literatures about the medication advancement on gastrointestinal polyposis of PJS were reviewed and analyzed. The recent development of targeting drugs, especially the data of cyclooxygenase-2 selective inhibitors and rapamycin, were emphatically summarized. Results With the deep investigation of PJS and application of selective drugs, the medication of gastrointestinal polyposis in cases of PJS has got more advancement. The extensive use of synthetic cyclooxygenase-2 inhibitors and rapamycin in clinic developed a new way to treat gastrointestinal polyposis of PJS. Conclusion The cyclooxygenase-2 selective inhibitors and rapamycin have the following features: noninvasive, high selectivity and good curative effects. They have splendid prospects in the clinical treatment of gastrointestinal polyposis in patients with PJS and are bring the treatment of gastrointestinal polyposis in cases of PJS into a targeting therapy phase.