The main treatment approach for gastrointestinal malignancies still involves surgical procedures complemented by radiotherapy and chemotherapy. However, the high recurrence and low 5-year survival rates after surgery have become significant issues affecting the life and health of patients. In contrast to traditional conventional treatments involving surgery followed by radiotherapy and chemotherapy, neoadjuvant therapy is a treatment method that moves radiotherapy, chemotherapy, interventional therapy, targeted therapy, and immunotherapy to preoperative period. It offers advantages such as improving radical resection rate, prolonging survival, and enhancing the quality of life. Because it is difficult to significantly extend the survival of patients with gastrointestinal malignancies through traditional conventional treatments, the advantages of neoadjuvant therapy have become increasingly apparent in the treatment of various malignant tumors. It is gradually being included in the recommended treatment standards of the latest authoritative clinical guidelines. Immune checkpoint inhibitors (ICIs) are a new class of anti-tumor immunotherapy drugs that activate the immune system to attack tumor cells by blocking immune checkpoints. This category includes programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors, as well as cytotoxic T-lymphocyte-associated protein 4 (CTAL-4) inhibitors. The development and application of ICIs have brought new hope to countless cancer patients and are considered groundbreaking in the field of medical oncology. ICIs have been widely used in the comprehensive treatment of gastrointestinal malignancies. The combination of chemotherapy and immunotherapy, as well as immunotherapy alone, has shown significant effects in patients with advanced, unresectable, or metastatic gastrointestinal malignancies. It has become one of the treatment choices for these patients. This provides a promising opportunity for the use of ICIs in the neoadjuvant treatment of locally resectable or potentially resectable gastrointestinal malignancies. Recent results from phase I/Ⅱ clinical trials indicate that neoadjuvant immunotherapy based on ICIs holds great potential in the treatment of gastrointestinal malignancies. It significantly reduces tumor stage, and increases the pathological remission and complete resection rates, with controllable safety. However, the long-term survival outcomes still require further observation, and more phase Ⅲ studies are needed to elucidate the effectiveness of ICIs in neoadjuvant treatment of gastrointestinal malignancies. Here, the authors analyze and discuss the current clinical applications of ICIs in the neoadjuvant treatment of gastrointestinal malignancies, recent clinical research findings, and potential mechanisms of action.