Background Prescriptions of semaglutide, a glucagon-like peptide-1 receptor agonist administered weekly for Type 2 diabetes mellitus and obesity, are increasing. Adverse effects from semaglutide overdose are poorly described. We report adverse effects from three unintentional semaglutide overdoses upon initiation. Case reports Case 1 : A 53-year-old man unintentionally injected semaglutide 2 mg instead of the recommended 0.1 mg. Case 2 : A 45-year-old woman unintentionally injected semaglutide 2.4 mg instead of 0.25 mg. Case 3 : A 33-year-old woman injected semaglutide 1.7 mg. All three of these patients developed nonspecific gastrointestinal symptoms. No patient experienced hypoglycemia. Discussion These unintentional semaglutide overdoses occurred due to deficits in patient and prescriber knowledge, and evasion of regulated access to pharmaceuticals. Nonspecific gastrointestinal symptoms predominated. The potential for hypoglycemia following glucagon-like peptide-1 agonist overdose is unclear, though it did not occur in our patients. It is thought that glucagon-like peptide-1 agonists are unlikely to cause hypoglycemia because their effects are glucose-dependent and diminish as serum glucose concentrations approach euglycemia. There is, however, an increase in hypoglycemia when glucagon-like peptide-1 agonists are combined with sulfonylureas. Conclusions This case series highlights the critical role of patient education and training upon initiation of semaglutide therapy to minimize administration errors and adverse effects from injection of glucagon-like peptide-1 receptor agonists.