Surgical resection is the most effective method for craniopharyngioma, with complex operations and a high incidence of complications, especially for complex craniopharyngioma. The study focuses on selecting a proper surgical method to treat complex craniopharyngioma. A clinical study was conducted in this direction to explore the efficacy of expanded endoscopic endonasal transsphenoidal approach (EETS) and transcranial approach (TCA) in the treatment of complex craniopharyngioma and their effects on pituitary function and complications of patients. The clinical data of 73 patients with complex craniopharyngioma in Baoding No.2 Central Hospital from December 2017 to December 2022 were retrospectively analyzed. 13 patients who did not meet the admission criteria were excluded, and 60 patients were finally included. The included patients were divided into the TCA and EETS groups according to the treatment method. The surgical conditions, total tumor resection rate, clinical remission rate, and complications of patients in two groups were compared. The pituitary function of all patients, including thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and human growth hormone (hGH), was compared. A total of 60 patients were finally included in the study, including 30 cases in the EETS group and 30 cases in the TCA group. The two groups had no statistical difference in baseline demographic characteristics and pathological types (p > 0.05). Compared with the TCA group, the EETS group had less intraoperative blood loss, operation time, tumor resection time, and hospitalization time (p < 0.001) and had a significantly higher total tumor resection rate and clinical remission rate (p < 0.05). The EETS group had higher ACTH and hGH levels than the TCA group (p < 0.05). There was no statistical difference between the two groups incidence of complications and disease recurrence rate (p > 0.05). The craniopharyngioma resection via EETS has a significant therapeutic effect in complex craniopharyngioma with a high total tumor resection rate and clinical remission rate, which can protect the pituitary function of patients and provide more benefits for patients.