A large overdose of insulin is a serious health matter. Information concerning administration and duration of intravenous (IV) glucose, other treatment options or complications besides hypoglycaemia following large insulin overdoses is not readily apparent from the literature. A systematic search, compilation and review of case reports on insulin overdoses, published 1986-2017, was performed in PubMed, EMBASE, Cochrane and PROSPERO databases. Of 1523 published articles, 45 cases of insulin overdoses were included with a total median insulin dose of 900 international units (IU) (range 26-4800 IU). Hospitalization occurred in 44 cases with a median hospitalization duration of 94 hr (range 12-721 hr), and one-third (n = 15) admitted to the intensive care unit. First-line treatment was IV glucose treatment in 95% of cases. Treatment options besides IV glucose that were reported beneficial included glucagon IV or intramuscular (IM), octreotide IV or IM, surgical excision, hydrocortisone IV and oral intake of complex carbohydrates. Prevalent complications were intermittent cerebral impairment (73%), hypokalaemia (49%), other electrolyte disturbances (42%), and hepatic disturbances (7%) and cardiac toxicity (e.g. cardiac arrhythmia) (9%). Long-term consequences were one case of lasting hypoglycaemic encephalopathy and one death. In conclusion, following large insulin overdoses, in-hospital admission and treatment with IV glucose may be needed for up to a week. Monitoring of electrolytes and hepatic and cardiac functions seems important. Several experimental treatment options may be considered in addition to glucose administration. With appropriate pre- and in-hospital treatment, cases with severe hypoglycaemia and neurologic complications may have a favourable outcome.