Huntington’s Disease (HD) is a genetic neurodegenerative disease caused by a mutation in the huntingtin gene. Mutant huntingtin (mHtt) leads to cellular malfunction, mHtt aggregates and eventually neuronal death. HD patients show impaired motor functions and cognitive decline. Elevated levels of glucocorticoids have been found in patients and in HD mouse models, and antagonism of the glucocorticoid receptor (GR) may be an interesting strategy for the treatment of HD. Here, we tested the efficacy of CORT113176 in the commonly used R6/2 mouse model, characterized by severe motor and neurological decline in the course of weeks. In male mice, CORT113176 significantly delayed loss of grip strength, the development of hindlimb clasping, gait abnormalities, and the occurrence of epileptic seizures. While not preventing neurodegeneration in the striatum, CORT113176 did restore changed astrocyte markers in both striatum and hippocampus as well as microglia markers in hippocampus suggesting that CORT113176 has both cell- and region-specific effects. CORT113176 delayed the formation of mHtt aggregates in the striatum and the hippocampus. We conclude that CORT113176 effectively delays several key symptoms related to the HD phenotype in male mice. In view of the literature, this might reflect a generic mechanism by which GR antagonists can ameliorate neurodegenerative diseases.