The aims of this study were to evaluate the impact of anesthesia depth on postoperative serum Adiponectin (ADP), MMP-9, S-100β protein concentration, and Postoperative Cognitive Dysfunction (POCD) in elderly patients with general anesthesia. A total of 120 elderly patients undergoing elective gastrointestinal surgery under general anesthesia were divided into 2 groups: Group A (n=60) was applied Closed Loop Target Controlled Infusion (CLTCI) to maintain the Bispectral Index (BIS) value of Electroencephalograph (EEG) as 45, and Group B (n=60) maintain the BIS value of EEG as 55. The MoCA scores in the two groups were decreased by different degrees after surgery. The MoCA scores in Group B on d’s 1 and 3 after surgery were higher than Group A (P<0.05). The serum concentrations of MMP-9 and S-100β in the two groups were significantly higher at T1, T2, and T3 (P<0.05), but the serum ADP concentrations were decreased. The serum concentrations of MMP-9 and S-100β in group B were lower than group A (P<0.05), while the serum ADP level was higher than group A (P<0.05). The anesthesia depth with the BIS value as 55 has less impairment toward the early postoperative cognitive function in elderly patients than that with BIS as 45, which may be related to the increased serum ADP and decreased serum MMP-9 levels.