Depression is a common mental disorder primarily characterized by a persistent low mood. Clinically, patients with depression often suffer from insomnia, which has become more prevalent since the COVID-19 pandemic due to the dual pressures of life and work. Insomnia and depression frequently cooccur as dual symptoms. Traditional treatments involving a combination of antidepressant and anti-insomnia medications can be effective, but they have significant adverse effects and numerous usage limitations. Therefore, there is an urgent need for research into the shared targets of both conditions and the development of new therapeutic approaches for comorbid depression and insomnia. This review explores the role of orexin, its receptor signaling pathway and its distribution in the brain, and discusses the connections between orexin and the comorbidity of insomnia and depression, along with potential targets and mechanisms. This article highlights the possibility of orexin in treating comorbid depression and insomnia, aiming to provide a reference for the development and application of orexin, and to better address the issue of comorbid depression and insomnia.