Objective: This study aimed to explore the clinical application effects of fast-track surgery (FTS) in patients undergoing total gastrectomy during the perioperative period, to provide a foundation for the application of FTS during the gastrointestinal surgery perioperative period. Methods: A total of 50 gastric cancer patients undergoing total gastrectomy were selected as clinical research objects. 25 of the patients were nursed routinely as a control group, and 25 patients were nursed as an observation group following instructions based on fast-track surgery. The two groups' intraoperative blood loss, operation times, drainage tube extubating times, and C-reactive protein content at 3 days after surgery were analyzed and compared. Their differences in the first anal exhaust times, intestinal sound recovery times, hospitalization times, operation costs, and postoperative complications were also evaluated and recorded after surgery. Results: Both groups were cured and discharged smoothly. Compared with the control group, the observation group showed significantly better performance in intraoperative blood loss, drainage tube extubating times, and C-reactive protein content at the third day after surgery (all P<0.001), and there was no significant difference between the two groups in operation times (P>0.05). The observation group nursed under instructions based on FTS experienced a significantly earlier first anal exhaust, a faster recovery of intestinal sound, and a shorter hospitalization time, showed a lower postoperative complication rate, and had significantly lower operation costs than the control group (all P<0.05). Conclusion: Because it is able to reduce intraoperative trauma and complications, speed up the postoperative recovery rate, and improve the treatment satisfaction of patients, FTS has definite clinical value and safety for patients with gastric cancer undergoing total gastrectomy during the perioperative period.