The dual GLP-1/GIP receptor agonist “twincretin” was evaluated for neurotrophic and neuroprotective actions in cell and in vivo models of mild TBI. Twincretin provided neurotrophic properties in immortal human SH-SY5Y neuronal cells - elevating cAMP levels and pCREB. Twincretin provided neuroprotection against oxidative stress and glutamate excitotoxicity in human SH-SY5Y cells. Twincretin protected rat primary cultures of dopaminergic ventral mesencephalon neurons from 6-hydroxydopamine-induced injury. A clinically translatable dose of twincretin fully mitigated mild TBI-induced spatial and visual memory deficits in a mouse close head injury model. Twincretin mediated mitigation of cellular and in vivo TBI-induced impairments highlight the agent for evaluation in neurodegenerative disorders.