Propofol and sevoflurane are commonly used anesthetic agents for maintenance anesthesia during radical resection of gastric cancer. However, there is a debate concerning their differential effects on cognitive function, anxiety, and depression in patients undergoing this procedure. To compare the effects of propofol and sevoflurane anesthesia on postoperative cognitive function, anxiety, depression, and organ function in patients undergoing radical resection of gastric cancer. A total of 80 patients were involved in this research. The subjects were divided into two groups: Propofol group and sevoflurane group. The evaluation scale for cognitive function was the Loewenstein occupational therapy cognitive assessment (LOTCA), and anxiety and depression were assessed with the aid of the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Hemodynamic indicators, oxidative stress levels, and pulmonary function were also measured. The LOTCA score at 1 d after surgery was significantly lower in the propofol group than in the sevoflurane group. Additionally, the SAS and SDS scores of the sevoflurane group were significantly lower than those of the propofol group. The sevoflurane group showed greater stability in heart rate as well as the mean arterial pressure compared to the propofol group. Moreover, the sevoflurane group displayed better pulmonary function and less lung injury than the propofol group. Both propofol and sevoflurane could be utilized as maintenance anesthesia during radical resection of gastric cancer. Propofol anesthesia has a minimal effect on patients' pulmonary function, consequently enhancing their postoperative recovery. Sevoflurane anesthesia causes less impairment on patients' cognitive function and mitigates negative emotions, leading to an improved postoperative mental state. Therefore, the selection of anesthetic agents should be based on the individual patient's specific circumstances.