This paper addresses the ventilation challenges arising from extreme low temperatures and complex tunnel structures in ultra-large underground cavern projects within cold regions. Aiming to enhance ventilation efficiency and ensure operational safety, it investigates optimised hybrid ventilation layout schemes. By establishing a three-dimensional numerical model of the meandering construction tunnel and validating its reliability through field measurements, the study systematically analysed the impact of three critical factors on the stability of the working face airflow field and the efficiency of CO pollutant removal: supply/extraction air volume distribution, extraction duct placement, and the overlap distance between supply and extraction ducts. Building upon this, the entropy weighting method was employed to determine objective weights for two metrics: the time required to reduce wind speed standard deviation and CO concentration to safe limits. Grey relational analysis was then applied to conduct a multi-objective comprehensive evaluation of 12 ventilation scenarios. Results indicate that wind speed uniformity and pollutant removal efficiency carry weights of 0.538 and 0.462 respectively, both significantly influencing ventilation effectiveness. The optimal ventilation scheme is Scenario 5, employing a ‘left supply, right extraction’ layout with a supply/extraction airflow ratio of 1.2, where ducts are positioned along the top of both tunnel sides. This scheme ensures stable airflow while achieving efficient and rapid CO removal, providing theoretical foundations and practical guidance for ventilation design in complex underground engineering projects in cold regions.