Lobetyolin, a polyacetylene glycoside derived from Codonopsis pilosula, is emerging as a promising natural candidate for Alzheimer’s disease prevention and healthy aging. In Aβ-expressing and wild-type Caenorhabditis elegans models, Lobetyolin significantly reduced β-amyloid deposition, delayed paralysis, lowered intracellular ROS levels, and extended lifespan. Integrated metabolomic and transcriptomic analyses identified glutathione-centered redox regulation as its principal mechanism, including selective modulation of GST isoforms such as gst-1 and gst-38. These redox improvements are consistent with reduced Aβ toxicity and enhanced stress resistance. Owing to its natural abundance in dietary materials like Codonopsis radix, Lobetyolin also holds potential as a food-derived neuroprotective factor. However, the lack of mammalian efficacy data and pharmacokinetic characterization currently limits translational interpretation. Future research should confirm therapeutic effects in rodent models, determine brain exposure and PK/PD profiles, and conduct comprehensive safety evaluations. Overall, this study provides mechanistic insight and a clear foundation for advancing Lobetyolin as a nutraceutical candidate for AD prevention and aging-related interventions.