Objective: To explore the impact of nociception level (NOL) index guidance on the occurrence of acute postoperative pain (APP) and gastrointestinal function recovery after laparoscopic appendectomy (LA) in patients with acute purulent appendicitis, to analyze the related factors of APP after LA in patients with acute purulent appendicitis. Methods: A total of 120 patients with acute purulent appendicitis who underwent LA were selected and divided into an observation group and a control group according to different anesthesia method using the random number method, 60 cases in each group. Both groups of patients were given combined intravenous-inhalation anesthesia and standard anesthesia care. The observation group used NOL to guide intraoperative analgesia, while the control group adjusted the concentration and dose of analgesic drugs according to changes in hemodynamic parameters during the operation. The stress response indicators Cor, E, NE, and inflammatory indicators TNF-α, IL-1β, IL-6 levels of the two groups of patients were detected 2 hours before surgery and 60 minutes after surgery. The occurrence of emergence agitation, APP, and intraoperative remifentanil dose of the two groups of patients were recorded. The gastrointestinal function recovery time of the two groups of patients was observed. All patients were divided into APP group and non-APP group according to whether APP occurred, and the clinical data of the two subgroups were compared, and Logistic regression analysis was used to analyze the independent related factors of APP after LA in patients with acute purulent appendicitis. Results: At 60 minutes post-operation, the observation group exhibited lower levels of Cor, E, and NE compared to the control group, along with reduced inflammatory markers TNF-α, IL-1β, and IL-6 (P<0.05). The time to first flatus, first defecation, and first oral intake were shorter in the observation group (P<0.05). The incidence of emergence agitation (EA) and APP was lower in the observation group, accompanied by a reduced remifentanil dose (P<0.05). No statistically significant difference in adverse reactions was observed between the two groups (P>0.05). Logistic regression analysis showed that age (OR = 0.908, 95% CI: 0.851–0.961, P = 0.003) and NOL guidance (OR = 0.281, 95% CI: 0.099–0.799, P = 0.017) were independently associated with the occurrence of APP. Conclusion: NOL index guidance significantly decreases the incidence of APP in patients undergoing laparoscopic appendectomy while concurrently reducing intraoperative remifentanil consumption.