Colivelin is a potent synthetic peptide activator of STAT3 that has neuroprotective activity. It protects approximately 50 and 100% of mouse primary cortical neurons from cell death induced by amyloid β (1-43) (Aβ43) when used at concentrations of 10 and 100 fM, respectively. Colivelin protects against cell death induced by V642I-APP in a CaM kinase IV (CaMKIV) and STAT3-dependent manner. It increases STAT3 phosphorylation in vitro and in vivo, an effect that correlates with improvements in working memory. Colivelin (10 pmol every six days) rescues deficits in spatial working memory in a mouse model of Alzheimer’s disease induced by intracerebroventricular injection of Aβ25-35. It also improves motor performance and prolongs survival in a mouse model of amyotrophic lateral sclerosis (ALS).