BACKGROUND: Increasing evidence has shown that hippocampal damage serves as a marker of early cognitive decline in patients with type 2 diabetes mellitus (T2DM); however, the association between hippocampal subregion volume changes and cognitive decline in different dimensions remains unclear. AIM: To investigate changes in hippocampal subregion volumes in patients with T2DM and their relationship with cognitive function impairment. METHODS: Sixty patients with T2DM and 32 healthy controls were recruited. All participants underwent a 3.0 T magnetic resonance scan and a series of clinical assessments. Hippocampal subfield volumes were determined using FreeSurfer 7.4.1. A two-sample -test was used to evaluate group differences. Partial correlation analysis was performed to assess the relationship between hippocampal subregion volumes and cognitive function. < 0.05 was considered statistically significant. RESULTS: Compared with controls, the volume of right hippocampus-amygdala transition area ( = -3.053, = 0.003) in patients with T2DM was significantly reduced, which was negatively correlated with the required time of the Trail Making Test (TMT)-A ( = -0.331, = 0.028) and TMT-B ( = -0.402, = 0.007) and positively correlated with the scores of Symbol Digit Modalities Test ( = 0.381, = 0.011), Auditory Verbal Learning Test (AVLT)-N7 ( = 0.309, = 0.041), and Digital Span Test ( = 0.300, = 0.048). The volume of the right molecular layer ( = -2.998, = 0.004) was also significantly reduced, which was positively associated with the scores of AVLT-N7 ( = 0.311, = 0.045). In addition, the left hippocampal fissure volume ( = 3.617, = 0.002) was significantly increased in patients with T2DM. CONCLUSION: Declines in cognitive performance, especially memory and executive function, are linked to changes in the volumes of the right hippocampus-amygdala transition area and right molecular layer in patients with T2DM.