To explore the association between visceral adipose tissue (VAT) volume and gray matter volume in middle-aged and elderly population. Methods: This study utilized the UK Biobank resource. Multivariate linear regression models were used to analyze the correlation between VAT and gray matter volume, with covariates including age, sex, smoking, alcohol consumption, body mass index (BMI), waist-to-hip ratio, physical activity, HDL cholesterol, LDL, cholesterol, triglycerides, history of hypertension, diabetes, and cardiovascular disease. Results: A total of 23 310 participants, including 11 052 males and 12 258 females, were included in the final analysis. The multivariate linear regression model showed that VAT was independently correlated with gray matter volume even after adjusting for body fat factors such as BMI and waist-to-hip ratio (β=－2.04, 95%CI －3.24～－0.84, P=0.001). There were statistical differences in baseline characteristics, such as age, smoking and alcohol history, BMI, and waist-to-hip ratio, between male and female participants(P<0.001), with males having smaller gray matter volume [(810.82±45.90) cm3 vs. (777.88±44.64) cm3 , P<0.001] and higher VAT volume than females [(2.62±1.50) L vs. (4.90±2.31) L，P<0.001] . Subgroup analysis showed that only in males, VAT was independently correlated with gray matter volume (β=－2.95，95%CI －4.46～－1.44，P<0.001). Conclusion: VAT is negatively correlated with gray matter volume in middle-aged and elderly population, and this correlation is more apparent in males.To explore the association between visceral adipose tissue (VAT) volume and gray matter volume in middle-aged and elderly population. Methods: This study utilized the UK Biobank resource. Multivariate linear regression models were used to analyze the correlation between VAT and gray matter volume, with covariates including age, sex, smoking, alcohol consumption, body mass index (BMI), waist-to-hip ratio, physical activity, HDL cholesterol, LDL, cholesterol, triglycerides, history of hypertension, diabetes, and cardiovascular disease. Results: A total of 23 310 participants, including 11 052 males and 12 258 females, were included in the final analysis. The multivariate linear regression model showed that VAT was independently correlated with gray matter volume even after adjusting for body fat factors such as BMI and waist-to-hip ratio (β=－2.04, 95%CI －3.24～－0.84, P=0.001). There were statistical differences in baseline characteristics, such as age, smoking and alcohol history, BMI, and waist-to-hip ratio, between male and female participants(P<0.001), with males having smaller gray matter volume [(810.82±45.90) cm3 vs. (777.88±44.64) cm3 , P<0.001] and higher VAT volume than females [(2.62±1.50) L vs. (4.90±2.31) L，P<0.001] . Subgroup analysis showed that only in males, VAT was independently correlated with gray matter volume (β=－2.95，95%CI －4.46～－1.44，P<0.001). Conclusion: VAT is negatively correlated with gray matter volume in middle-aged and elderly population, and this correlation is more apparent in males.