Purpose There has been increasing interest in identifying non-invasive, imaging biomarkers for neurodegenerative disorders of the central nervous system (CNS). The aim of this proof-of-concept study was to investigate whether corneal sensory nerve and dendritic cell (DC) parameters, captured using in vivo confocal microscopy (IVCM), are altered in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods Fifteen participants were recruited from the Australian Imaging Biomarkers and Lifestyle (AIBL) study in Melbourne, VIC, Australia. The cohort consisted of cognitively normal (CN) individuals (n = 5), and those with MCI (n = 5) and AD (n = 5). Participants underwent a slit lamp examination of the anterior segment, followed by corneal imaging using laser-scanning in vivo confocal microscopy (IVCM) of the central and inferior whorl regions. Corneal DC density, field area, perimeter, circularity index, aspect ratio, and roundness were quantified using Image J. Quantitative data were derived for corneal nerve parameters, including nerve fiber length (CNFL), fiber density (CNFD), branch density (CNBD), and diameter. Results Corneal DC field area and perimeter were greater in individuals with MCI, relative to CN controls, in both the central and inferior whorl regions (p < 0.05 for all comparisons). In addition, corneal DCs in the whorl region of MCI eyes had lower circularity and roundness indices and a higher aspect ratio relative to CNs (p < 0.05 for all comparisons). DC density was similar across participant groups in both corneal regions. There was a trend toward lower quantitative parameters for corneal nerve architecture in the AD and MCI groups compared with CN participants, however, the inter-group differences did not reach statistical significance. Central corneal nerve diameters were similar between groups. Conclusion This study is the first to report morphological differences in corneal DCs in humans with MCI. These differences were evident in both the central and mid-peripheral cornea, and in the absence of significant nerve abnormalities or a difference in DC density. These findings justify future large-scale studies to assess the utility of corneal IVCM and DC analysis for identifying early stage pathology in neurodegenerative disorders of the CNS.