Mild Cognitive Impairment (MCI) is a precursor to Alzheimer's disease (AD), necessitating early identification through reliable markers. We employed ProteographTM, an automated platform utilizing nanoparticles coupled with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow, enabling comprehensive, unbiased detection of low-abundance proteins (LAPs) in plasma. We analyzed the plasma proteome from 42 MCI patients and 13 controls. A total of 35 differentially expressed proteins (DEPs) were identified, with significant correlations to Mini-Mental State Examination (MMSE) scores. Composite panels of candidate proteins exhibited potential for distinguishing MCI and its subtypes, providing insight into underlying pathophysiological mechanisms. Our findings identify novel blood protein candidates with potential to enhance early MCI diagnosis and provide insight into the progression of AD.