GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The preproglucagon neurons located in the brainstem can also produce GLP-1. GLP-1 analogs have a long-acting effect and are able to pass the blood-brain barrier, which probably extends the therapeutic efficacy of GLP-1R activation. Neurodegenerative or traumatic conditions can damage the spinal cord and result in motor and sensory dysfunction. Evidence supports that GLP-1R activation in the spinal cord possesses beneficial effects and significant therapeutic potential. Herein, we review studies that have focused on GLP-1 and the spinal cord, and summarize the expression of GLP-1R and the innervation of PPG neurons in the spinal cord, as well as the potential therapeutic benefits of GLP-1R activation.