This research sets out to elucidate the influence of comprehensive nursing intervention (CNI) on vital signs (VSs) and negative emotions (NEs) of patients with gastrointestinal polyps treated by digestive endoscopy. To address this, from January 2020 to February 2021, 92 cases of gastrointestinal polyps treated by digestive endoscopy in the Yuyao People’s Hospital of Zhejiang Province were partitioned into two different groups: the control group (CG; n = 46) intervened by routine nursing intervention, and the research group (RG; n = 46) treated by CNI based on routine care. The VSs, NEs, time of first postoperative exhaust and defecation, early food intake, length of stay (LOS), quality of life (QOL), nursing satisfaction, and the incidence of postoperative complications were compared between groups. When entering the operating room, elevated systolic/diastolic (SBP/DBP) was observed in CG compared with RG ( P < 0.05 ) while there was no statistical difference in SBP/DBP in RG before intervention and when entering the operating room ( P > 0.05 ). Statistically, less time of first exhaust and defecation as well as LOS and early food intake were observed in RG ( P < 0.05 ). The HAMA and HAMD scores declined in both arms postintervention, and the decrease was more obvious in RG ( P < 0.05 ). After intervention, the scores of various domains of GQOLI-74 elevated in both arms, and the increase was more obvious in RG ( P < 0.05 ). RG also showed a lower total complication rate and a higher degree of nursing satisfaction than CG ( P < 0.05 ). CNI for patients with gastrointestinal polyps treated by digestive endoscopy can obviously relieve their anxiety and depression, with stable VSs, short LOS, and low incidence of complications.