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Objective: The purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States. Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011–2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted. Results: The RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (β:-0.76, P<0.05) and Digit Symbol Substitution tests (β:-5.02, P<0.05). Nevertheless, these results showed marginal significance in Total Word Recall test as well as Animal Fluency test. Among all subgroup analyses performed, participants with both abnormal SII levels and diabetes exhibited the greatest decline in cognitive function compared to those with only diabetes. Furthermore, KM curve demonstrated that the combination of abnormal SII levels and diabetes decreased survival rate among participants. Conclusion: The findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power. [ABSTRACT FROM AUTHOR]