OBJECTIVE To exc avate the adverse drug event （ADE）signals of semaglutide and provide reference for its clinical rational use. METHODS The proportional unbalance method was used to mine the signals of all semaglutide ADE reports from FDA Adverse Event Reporting System （FAERS）up to September 2021. The basic situations of the reported cases were analyzed. The corresponding system organ classification （SOC）was mapped and compared with the adverse drug reactions recorded in the drug instructions. Preferred terms （PT）of patients with different indications were analyzed. RESULTS A total of 6 661 semaglutide ADE reports were extracted and 194 valid signals were mined. Among 6 661 cases of ADE ，the proportion of men （43.40％）was lower than women （52.65％）；the age was mainly distributed in ＞40-65 years old （29.00％）and ＞65 years old （22.61％）；the reporting country was mainly the United States （83.88％）；the report year was mainly concentrated in 2021 （40.88％），with an increasing trend year by year ；the main outcome was hospitalization or prolonged hospitalization in serious ADE reports （17.78％）. Semaglutide ADE signal was mapped to the main SOC ，mainly including gastrointestinal diseases ，various injuries，poisoning and operation complications ，metabolic and nutritional diseases ，various examinations. The screening criteria were based on the report odds ratio ＞10 or ADE reported cases ＞50，and 48 new potential adverse drug reactions were added to the drug description. Among the indications with the top two reported cases （type 2 diabetes and obesity ，overweight，weight control），the frequency of gastrointestinal system related ADE reports represented by nausea ，vomiting and diarrhea was higher ， which was similar to the drug instructions. CONCLUSIONS This study supplemented 48 new potential adverse drug reactions based on the drug instructions of semaglutide. At present ，it can be considered that semaglutide is safe.