BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained popularity in recent years. Consequently, Semaglutide prescription rates have increased for both its indicated and off-label uses. A possible link between GLP-1 RAs and suicidal behavior has been proposed. CASE REPORT We describe a rare case of suicide-related behavior, adverse outcomes, and a self-injected Semaglutide overdose in a 67-year-old man with diabetes mellitus and overweight. The patient had been on a weekly 1-mg Semaglutide regimen for 1 year prior to hospitalization. He presented with multiorgan failure, hypoglycemia, cholestatic liver dysfunction, and 2 duodenal ulcers, and reported weakness, appetite loss, epigastric pain, severe diarrhea, and melena over 2 weeks, and syncope the day before admission. His clinical status improved gradually, including duodenal ulcers upon discharge. In further questioning, the patient recalled feeling moody and injecting his monthly Semaglutide prescription all at 1 time, 14 days before admission. The self-injection of an overdose 4 times greater than permitted may be considered suicidal behavior for 6 reasons: (1) Semaglutide treatment began more than 1 year before the event; (2) The patient was experienced in self-injecting; (3) A single injection is limited to the weekly recommended dose; (4) If multiple injections exceed the pre-filled monthly amount, an overdose might occur; (5) Semaglutide application by pen is very safe; and (6) He reported being dysphoric prior to the event. CONCLUSIONS Patients receiving GLP-1 Ras, such as Semaglutide, should be screened for common mental disorders in clinical practice. Also, we suggest multiorgan failure should be excluded in Semaglutide-treated patients with acute illness onset.