Abstract: Panax ginseng, a venerable herb in traditional Chinese medicine, boasts a rich history of usage in the treatment of dementia, particularly in its various manifestations. However, despite its long-standing popularity and empirical evidence of effectiveness, the precise mechanisms underlying its therapeutic actions have remained elusive. Currently, research on pharmacodynamic components and mechanisms predominantly utilizes serum pharmacology and metabolomics research methods that are based on liquid chromatography-mass spectrometry technology. However, these methods are unable to capture the spatial distribution information of relevant substances, leading to a lack of comprehensive understanding of the pharmacodynamic components and their underlying mechanisms. To bridge this gap in knowledge, a method of spatial metabolomics and air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), was used to delve into the molecular mechanisms of Panax ginseng in treating Alzheimer’s disease (AD). The pharmacodynamic results demonstrated that Panax ginseng extract can significantly improve the state of brain pathological damage and spatial learning memory ability in AD model rats. This finding highlights the potential of ginseng as a therapeutic agent in AD management. Furthermore, the metabolomics analysis revealed that Panax ginseng modulates the levels of 19 biomarkers that are intricately linked to AD. These biomarkers span across 8 key metabolic pathways, including arginine and proline metabolism, purine metabolism, the tricarboxylic acid (TCA) cycle, and fatty acid metabolism. These pathways are essential for maintaining neuronal health and function, and their dysregulation is often associated with the pathogenesis of AD. Importantly, the study identified 7 active ginseng constituents that accumulate in brain tissue. These compounds work in a holistic manner to treat AD by modulating metabolites related to neuroinflammation, neuronal damage, energy deficits, and abnormal fatty acid metabolism. The comprehensive approach suggests that Panax ginseng may offer a multifaceted therapeutic strategy for AD. The unique capabilities of mass spectrometry imaging allow to analyze the spatial distribution of both endogenous and exogenous substances in parallel. This correspondence not only provides a deeper understanding of the specific effects of drug components, but also sheds light on how these components interact with the body’s endogenous metabolic networks to exert their therapeutic effects. In conclusion, the study provides new light on the mechanisms of action of Panax ginseng in treating AD and paves the way for future research and clinical applications of the ancient herb.