Objective To explore the clinical comprehensive therapy of Peutz-Jeghers syndrome. Methods From January 2000 to December 2010，71 cases of Peutz-Jeghers syndrome underwent endoscopic polyp resection firstly，and those with unresectable lesions or with severe complications underwent rescue laparotomy. After endoscopic or surgical treatment，the patients took Celecoxib capsules voluntarily for 6 to 9 months under informed consents. All cases were followed up from 6 months to 8 years. Results Twenty-nine patients had familial history of Peutz-Jeghers syndrome among the 71 patients （41 males and 30 females）. Sixty-two cases underwent 94 surgeries and intussusception was the most common cause of laparotomy. Sixty-five patients underwent 169 double-balloon endoscopy （DBE） therapies，and a total of 1 714 polyps were resected by DBE polypectomy. The largest major axis of small-bowel polyp was 8 cm. No severe complications occurred after DBE polypectomy except for 3 cases of intestinal perforation. Eight patients took Celecoxib capsule，3 of them were treated more than 6 months，and DBE examination showed the gastrointestinal polyps reduced in number and size. Conclusion The comprehensive treatment （including of endoscopic therapy，operation，and drug intervention） is a safe and effective clinical model to treat Peutz-Jeghers syndrome．