Alcohol fuels, produced from renewable energy sources, are considered a crucial solution for achieving life-cycle carbon neutrality in internal combustion engines. The Boosted Uniflow Scavenged Direct-Injection Combustion Engine (BUSDICE) exhibits significant potential for high thermal efficiency with an aggressive downsizing design. In this study, a computational investigation was carried out to assess the spray mixing and combustion characteristics of BUSDICE fuelled with methanol and ethanol, compared with gasoline, under a high-load condition. The injection duration of methanol and ethanol is significantly longer than that of iso-octane, leading to incomplete evaporation. The mixture exhibits an “outer-rich, central-lean” stratification pattern due to the short mixing time and swirl flow transportation for all three fuels. However, the prolonged injection of methanol induces stronger turbulence, which can enhance the local mixing. The spatial mixture stratification, particularly near the spark-local area, has a strong influence on the initial kernel development and flame propagation. Consequently, methanol exhibits a shorter ignition delay than ethanol under the same spark timing, leading to faster flame propagation attributed to a richer equivalence ratio around the spark plug. Nevertheless, the ignition and combustion performance of ethanol can be improved by advancing the spark timing. The spark timing study reveals that alcohol fuels can operate under high load without knocking, whereas iso-octane requires retarded ignition timing to prevent knocking. As a result, methanol and ethanol provide a better IMEP and ITE than iso-octane under high-load conditions. From an emissions perspective, due to their low carbon-to-hydrogen (C/H) ratio and high oxygen content, unburnt hydrocarbon emissions decrease significantly when using alcohol fuels, especially methanol, for which these emissions are almost zero. However, the soot of ethanol shows a slight increase than iso-octane, due to the highly stratified mixture and incomplete combustion. Additionally, the NOx of ethanol and methanol increases due to the higher combustion temperatures than iso-octane. Overall, the results highlight the strong potential of alcohol-fuelled BUSDICE engines as compact and sustainable solutions for small-displacement powertrains, offering high thermal efficiency and substantially reduced pollutant emissions.