Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed as drugs for type 2 diabetes and obesity, exhibit therapeutic effects for various neurological disorders recently, with multiple neuroprotective mechanisms. The GLP-1RAs therapy has been applied to acute ischemic stroke, where they limit neuroinflammation, stabilize the neurovascular unit, and reduce infarct volume. The GLP-1RAs drugs have also been tested for Wolfram syndrome, where they mitigate endoplasmic reticulum (ER) stress and inhibit neuronal apoptosis. Preclinical analyses demonstrate that GLP-1RAs can modulate neuroinflammation processes, including reprogramming of microglia towards antiinflammatory phenotypes, suppression of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasome activation, suppressing pathological astrogliosis, and rebalance of peripheral immunity. Furthermore, GLP-1RAs were identified to enhance synaptic plasticity, improve cognitive deficits, and promote hippocampal neurogenesis via regulation of brain-derived neurotrophic factor/cAMP response element-binding protein (BDNF/CREB) and insulin-like growth factor 1 (IGF-1) pathways. However, embedded multimodal biomarkers (e.g., TREM2, neuroimaging, and neurogenesis markers) are required for further clinical translation and clinical trial investigation of target engagement, dosage optimization, and patient stratification. Future prioritizing mechanism-focused studies in the niche will help unlock the potential of GLP-1RAs as disease-modifying therapies for human neurological disorders.