Background Previous studies revealed that subcortical nuclei were harmed in the process of Alzheimer's disease (AD). Purpose To investigate the volumetric and diffusion kurtosis imaging (DKI) parameter changes of subcortical nuclei in AD and their relationship with cognitive function. Materials and Methods A total of 17 mild AD patients, 15 moderate to severe AD patients, and 16 controls underwent neuropsychological tests and magnetic resonance imaging (MRI) scans. Volume, mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) were measured in hippocampus, thalamus, caudate, putamen, pallidum, and amygdala. MRI parameters were compared. Correlation analysis was performed between subcortical nuclei volume, DKI parameters, and MMSE score. Results Significant volume reduction was seen in the left hippocampus in mild AD, and the bilateral hippocampus, thalamus, putamen, left caudate, and right amygdala in moderate to severe AD ( P < 0.05). Increased MD values were observed in the left hippocampus, left amygdala, and right caudate in mild AD, and the bilateral hippocampus and right amygdala in moderate to severe AD ( P < 0.05). Decreased MK values were observed only in the bilateral hippocampus in moderate to severe AD ( P < 0.05). No group significances were found in FA value. MMSE score was positively correlated with the volume of the bilateral hippocampus, thalamus, and putamen, and MK value of the left hippocampus ( P < 0.05). A negative correlation was found with the MD value of the bilateral hippocampus and left amygdala ( P < 0.05). Conclusion Mild AD mainly has microscopic subcortical changes revealed by increased MD value, and moderate to severe AD mainly has macroscopic subcortical changes revealed by volume reduction. MK is more sensitive in severe AD than mild AD.