Background <p>During laparoscopic cholecystectomy, pneumoperitoneum reduces pulmonary compliance, which may result in atelectasis and postoperative hypoxia. The efficacy of laryngeal mask ventilation during laparoscopic surgery is currently up for dispute. The objective of this study is to determine whether a Laryngeal Mask Airway Supreme™ (LMA-S) is non-inferior to an endotracheal tube (ETT) in maintaining lung compliance among low-risk patients undergoing laparoscopic cholecystectomy. The findings could be applied to implement novel airway management strategies for laparoscopic cholecystectomy procedures.</p> Methods <p>A total of 100 American Society of Anaesthesiologists Classification (ASA) I–II patients will be randomly allocated to airway management with an LMA-S (L group, <i>n</i> = 50) or an ETT (T group, <i>n</i> = 50). After the induction of general anaesthesia, patients in group L will receive LMA-S, while patients in group T will receive ETT. Lung-protective ventilation strategy (LPVS) will be employed throughout the procedure in both groups. The primary outcome is pulmonary dynamic compliance (Cdyn) 15 min after pneumoperitoneum and up-head position. Secondary outcomes include the oxygenation index (OI), peak inspiratory pressure (PIP), end-expiratory carbon dioxide (EtCO₂), Richmond Agitation-Sedation Scale (RASS) scores, perioperative hemodynamics, and adverse respiratory events.</p> Discussion <p>This study will evaluate the effects of LMA-S ventilation on Cdyn and oxygenation in patients undergoing laparoscopic cholecystectomy. Clinical evidence to optimize airway management strategies for low-risk patients undergoing laparoscopic cholecystectomy will be provided by the results.</p> Trial registration <p>China Clinical Trial Registry (ChiCTR2400083333). Registered 22 April 2024, <a href="https://www.chictr.org.cn">https://www.chictr.org.cn</a>.</p>