RAGE/SERT-IN-1 is a potent and orally active advanced glycation end products (RAGE) and serotonin transporter (SERT) inhibitor with IC 50 s of 8.26 μM and 31.09 nM, respectively. RAGE/SERT-IN-1 exhibits significant neuroprotective effect against Aβ 25-35 -induced neuronal damage and alleviates depressive behavior of mice. RAGE/SERT-IN-1 can be used for researching the comorbidity of Alzheimer's disease and depression.