We evaluated the neurotrophic and neuroprotective actions of OXM in neuronal cultures and in an ischemic stroke model. OXM provided neurotrophic properties in immortal human SH-SY5Y neuronal cells - elevating cAMP levels and pCREB. OXM provided neuroprotection against glutamate excitotoxicity and oxidative stress injury in SH-SY5Y cells and rat primary neurons. OXM actions were primarily mediated by the GLP-1R but not GCGR, and involved the PKA and MAPK but not PI3K pathway. OXM significantly reduced cerebral infarct size and improved locomotor activities in a transient MCAo rat model of stroke.