During past decades, the Great South of Madagascar is known to be facing persistent and severe drought. Thus, this study investigated the characteristics of future hydrological droughts (2025–2099) in this particular region under three emission scenarios that is the Shared Socio-economic Pathways (SSP) 1–2.6, SSP2-4.5, and SSP5-8.5 for three time periods of 24 years namely near future (NF, 2025–2049), mid-future (MF, 2050–2074), and far future (FF, 2075–2099). For that, monthly precipitation and minimum and maximum temperature from six global climate models (GCMs) from the Coupled Model Intercomparison Project phase 6 were downscaled with Bias-Correction Spatial Disaggregation (BCSD). The drought characteristics were identified using the Standardized Precipitation Evapotranspiration Index-12 (SPEI-12) and the run theory. The results showed that thanks to the BCSD, corrected GCMs showed better agreement with observed data (1950–2014) from ERA5. The results also suggested that the number of drought events per decade in the south of Madagascar will significantly increase starting from the middle of this century. Overall, droughts in the Great South will become shorter (less than 12 months), except under SSP5-8.5 in the FF with an average duration of 14 months. Starting from the MF, the Great South will suffer from more intense and severe drought, particularly under SSP5-8.5. Furthermore, the drought frequency in the region will rise in the future. The number of drought events that start during the early rainy season will also increase which may significantly impact the food security in the region. The findings of this study can help policymakers tailor climate adaptation strategies, water management policy, and food policy.