The wave run-up and air-gap responses of semi-submersible platforms under extreme sea conditions are crucial design considerations for ensuring the structural integrity and safety of marine engineering operations. This study investigated the impact of rogue waves on the wave run-up and air-gap responses of semi-submersible platforms using a transient focusing wave group to accurately simulate irregular seas. Comparative model tests were conducted on a semi-submersible platform under both rogue and non-rogue-wave conditions. The platform motions and air-gap responses were analysed using spectral analysis, extreme-value statistics, and wavelet methods. Rogue waves were found to significantly affect the air-gap response spectrum, increasing the nonlinearity of both the wave run-up and air-gap responses. Different locations on the platform exhibited varying statistical and spectral response characteristics. Rogue waves modified the instantaneous properties of wave elevation, thereby increasing the energy levels in the system. This study confirmed that rogue waves significantly influence the air-gap responses and wave run-up of semi-submersible platforms, suggesting that they should be considered when designing and planning the operations of these platforms. This study offers a comprehensive understanding of the complex interactions between rogue waves and large maritime structures and provides insights for improving safety and performance under extreme sea conditions.