Objective: To explore the impact of nociception level index (nociception level, NOL) guidance on the occurrence of acute postoperative pain (acute postoperative pain, APP) and gastrointestinal function recovery after laparoscopic appendectomy (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 from April 2024 to May 2025 in our hospital were selected and randomly divided into an observation group and a control group (each with 60 cases) using the random number method. Both groups of patients were given combined intravenous and inhalation anesthesia and standard anesthetic nursing, and the observation group used NOL guidance for intraoperative analgesia. 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 dosage 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 significantly 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 dosage (P<0.05). No statistically significant difference in adverse reactions was observed between the two groups (P>0.05). Logistic regression analysis identified age (OR=0.908) and NOL guidance (OR=0.281) as independent factors associated with APP occurrence (P<0.05). Conclusion: NOL guidance significantly decreases the incidence of APP in patients undergoing laparoscopic appendectomy while concurrently reducing intraoperative remifentanil consumption.