Background: Ginseng is a representative functional food for brain health. However, its active ingredient is not well defined. Gintonin is a novel material isolated from white/red ginseng and its lysophosphatidic acid (LPA) plays as an exogenous G protein-coupled LPA receptor (LPAR) agonist. Korean red ginseng marc (KRGM) is a by-product after KRG extractions. Purpose: In previous study, we demonstrated that KRGM-derived gintonin (KRGM-G) contains LPA C18:2, which is a major functional component, as much as white and/or red ginseng has. Methods: In present study, we further studied KRGM-G-mediated anti-Alzheimer’s disease (AD) effects using 5xFAD transgenic mice model for AD and SH-SY5Y cells. Results: KRGM-G improved cognition impairment in 5xFAD mice associated with alleviation of amyloid-β accumulation in the brain (hippocampus and cortex). KRGM-G inhibited activation of inflammatory cells (Iba-1-positive microglia and GFAP-positive astrocyte) and expression of pro-inflammatory mediators (IL-1β, IL-6, iNOS, or NO) in the brain of 5xFAD mice and cell viability in H2O2-induced SH-SY5Y cells, in agreement with down-regulation of p38 MAPK, NF-κB p65, and STAT3 signaling pathways. KRGM-G also prevented formation of reactive oxygen species and stimulated Nrf2-HO-1/4-HNE signaling pathway in the brain of 5xFAD mice and SY-SY5Y cells. Interestingly, these positive effects of KRGM-G on AD-related symptoms and immunopathology was associated with down-regulation of LPAR1 in the brain of 5xFAD mice. Conclusion: These results suggest that KRGM-G may improve AD-related cognitive dysfunction by stimulating anti-oxidant pathway (Nrf2) and inhibiting inflammatory pathways (p38/NF-κB/STAT3) through LPAR1.