Abstract Opioids are commonly used drugs in the clinic, mainly targeting different subtypes of opioid receptors distributed in central and peripheral neurons. They are the preferred drugs for treating acute pain or cancer pain. Delta opioid receptor(DOR) agonists are opioid drugs that target the delta opioid receptor. In recent years, they have received widespread attention due to their ability to improve ischemia/reperfusion injury in multiple organs such as the heart, brain, and liver, as well as their potential for treating mental and neurological disorders. This review summarizes the mechanism research of DOR agonists in treating a variety of diseases, prospects their clinical application prospects, and finds that DOR agonists may exert anti-ischemia/reperfusion injury effects on organs by reducing apoptosis and mitochondrial damage, and activating various signaling pathways; they also exhibit anti-inflammatory, antidepressant, and therapeutic effects on neurodegenerative diseases, providing a new perspective for the application of DOR agonists in treating related diseases.