Background <p>SOUL-tang has been clinically used to treat Alzheimer’s disease (AD) in South Korea, but its scientific efficacy remains unclear. Clarifying its neuroprotective effects and underlying mechanisms is essential for evaluating its potential as a therapeutic agent for AD.</p> Objective <p>This study aimed to investigate the neuroprotective effects of SOUL-tang and its active component, isoacteoside (ISO), in human neuroblastoma SH-SY5Y cells and an animal model using the forced swimming test (FST).</p> Results <p>SOUL-tang and ISO protected SH-SY5Y cells from amyloid-β (Aβ)-induced damage by preventing cell death and reducing lactate dehydrogenase and inflammatory cytokine levels. In the FST, they reduced immobility time and decreased AD-inducing factors (Aβ and total tau proteins) while increasing neuroprotective factors (brain-derived neurotrophic factor and cyclic adenosine monophosphate response element-binding protein) in the hippocampus. Additionally, SOUL-tang and ISO alleviated oxidative stress by enhancing superoxide dismutase activity and reducing malondialdehyde levels. They also modulated inflammatory responses by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. Furthermore, hippocampal neurotransmitter levels were significantly improved without inducing adverse effects.</p> Conclusion <p>These findings demonstrate that SOUL-tang exhibits neuroprotective effects by attenuating harmful substances associated with AD. Therefore, SOUL-tang may be a promising therapeutic candidate for AD and other neurodegenerative disorders, with potential translational value for clinical application.</p>