Objective To explore the influencing factors of β2 microglobulin (β2M) and its correlation with cognitive function in the elderly patients with diabetes mellitus. Methods A total of 300 elderly diabetic patients hospitalized in the departments of endocrinology and geriatrics of Xuanwu Hospital from May 2018 to May 2019 were recruited in this study. General clinical data, inflammatory indicators, and results of biochemical tests were collected. The cognitive function was evaluated using Montreal cognitive assessment (MoCA). The patients were divided into high and low β2M groups (149 and 151 patients respectively) according to β2M level. Statistical analyses were performed using SPSS statistics 22.0. Data comparison between two groups was performed using t test, Mann-Whitney U test or Chi-square test depending on data types. The correlation of β2M level with clinical indicators was analyzed by Pearson correlation analysis and multiple liner regression analysis. Logistic regression analysis was employed to analyze the affecting factors of cognitive impairment (CI) in the elderly diabetic patients. Results Compared with the high β2M group, the low β2M group had younger age, shorter diabetic duration, and lower levels of interleukin 6 (IL-6), homocysteine (HCY), triglyceride (TG), creatine, blood urea nitrogen (BUN) and uric acid (P<0.05). Multiple linear stepwise regression equation showed that β2M had positive correlations with creatine, BUN, IL-6 and uric acid (P<0.05). Univariate logistic regression analysis indicated that age, β2M, stroke, creatine and BUN were risk factors for CI in elderly patients with diabetes mellitus(P<0.05). Multivariate logistic regression analysis suggested that age, β2M and stroke were independent risk factors of CI in the elderly patients with diabetes mellitus (P<0.05). Conclusion β2M in elderly patients with diabetes mellitus is not only associated with declining renal function, but also an independent risk factor of CI.