Analysis of saliva, plasma, and fecal samples from older adults with mild cognitive impairment revealed distinct lipid disruptions across body systems. MCI patients showed elevated oxidized triacylglycerols in saliva, reduced cholesteryl linoleate (CE 18:2) in plasma, and decreased fatty acid esters of hydroxy fatty acids in feces. Three specific fatty acids—α-linolenic acid, docosapentaenoic acid, and CE 18:2—demonstrated strong diagnostic potential in receiver operating characteristic analysis. This multi-fluid approach represents a significant advancement in early dementia detection, offering non-invasive alternatives to brain imaging or cerebrospinal fluid analysis. The finding that oxidative lipid damage appears in saliva before cognitive symptoms become severe suggests metabolic dysfunction precedes neuronal loss. However, this cross-sectional design cannot establish causation, and the sample size limits generalizability. The elevated medium-chain fatty acid triacylglycerols in feces point to gut-brain axis dysfunction, aligning with emerging research on microbiome contributions to neurodegeneration. While promising for clinical screening, these biomarkers require longitudinal validation to determine whether they predict progression from MCI to dementia.