Objective: To investigate the effect of anesthesia in elderly orthopedic surgery under the monitoring of bispectral index (BIS) and its effect on serum central nervous system specific protein β (S100β) level. Methods: A total of 104 elderly patients who underwent orthopedic surgery in Jiangyin Hospital of Traditional Chinese Medicine from February 2018 to February 2022 were randomly divided into a control group and a study group, with 52 cases in each group. The control group adjusted the depth of anesthesia according to the experience of the anesthesiologist and the clinical symptoms and signs of the patients, while the study group adjusted the depth of anesthesia according to the BIS monitoring data. The intraoperative dosage of main anesthetic drugs, postoperative recovery indicators, hemodynamic indicators at each time point, serum S100β level, Montreal Cognitive Assessment (MoCA) score, the Confusion Assessment Method (CAM) score changes, and the incidence of adverse reactions during recovery from anesthesia were compared between the 2 groups. Results: The dosage of sufentanil citrate injection and propofol injection in the study group was less than that in the control group, and the postoperative recovery time and extubation time were shorter than those in the control group (all P<0.05). The levels of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) at T1, T2, T3, and T4 in the study group were lower than those in the control group (all P<0.05). The serum S100β level and CAM score of the study group at 24 and 72 h after the operation were lower than those of the control group, and the MoCA score was higher than that of the control group (all P<0.05). The total adverse reaction rate during anesthesia recovery period in the study group was 5.77% (3/52), which was lower than that in the control group (P<0.05). Conclusion: The application of anesthesia under BIS monitoring to elderly orthopedic surgery can reduce the dosage of anesthetics, improve the hemodynamic level and cognitive function, reduce the level of serum S100β, promote postoperative recovery, and reduce adverse reactions.