There is a significant body of research undertaken in order to elucidate the mechanisms underlying the pathology of Alzheimer's disease (AD), as well as to discover early detection biomarkers and potential therapeutic strategies. One such proposed biomarker is the calcium binding protein S100β, which, depending on its local concentration, is known to exhibit both neurotrophic and neuroinflammatory properties in the central nervous system. At present, relatively little is known regarding the effect of chronic S100β disruption in AD. Dietary intake has been identified as a modifiable risk factor for AD. Preliminary in vitro and animal studies have demonstrated an association between S100β expression and dietary intake which links to AD pathophysiology. This review describes the association of S100β to fatty acids, ketone bodies, insulin, and botanicals as well as the potential impact of physical activity as a lifestyle factor. We also discuss the prospective implications of these findings, including support of the use of a Mediterranean dietary pattern and/or the ketogenic diet as an approach to modify AD risk.