Background: Diabetes mellitus is associated with a more severe course of coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes angiotensinconverting enzyme II (ACE2) receptor for host cell entry. We aimed to assess the interactions between antihyperglycemic drugs and the renin-angiotensin system (RAS) and their putative roles in COVID-19. Methods: A literature search was performed using Pubmed to review the interrelationships between hyperglycemia, RAS and COVID-19, and the effects of antihyperglycemic medications. Results: The RAS has an essential role in glucose homeostasis and may have a role in COVID-19-induced lung injury. Some antihyperglycemic medications modulate RAS and might hypothetically alleviate the deleterious effect of angiotensin II on lung injury. Furthermore, most antihyperglycemic medications showed anti-inflammatory effects in animal models of lung injury. Conclusions: Some antihyperglycemic medications might have protective effects against COVID-19- induced lung injury. Early insulin therapy seems very promising in alleviating lung injury.