The spinocerebellar ataxia type1 (SCA1) is a progressive rare neurodegenerative disease commonly associated with impairment of motor coordination and movement control. The cerebellar Purkinje neuron, spinal cord, and its connective tissues are the predominant affecting brain regions. The molecular pathology underlying SCA1 is known as accumulation of poly-glutamine (polyQ) expansion in ATXN1 gene. The interaction between ATXN1 and CIC plays a pivotal role in the pathogenesis of SCA1, particularly in cerebellar Purkinje cells. Recent findings have demonstrated phenotypic rescue through a mutant impeding the ATXN1-CIC interaction. In this study, we employed a Fluorescence Polarization (FP) system to identify small molecules obstructing this interaction, successfully discovering hits through High Throughput Screening (HTS). The structural analysis of ATXN1 in complex with hit compounds provide the molecular basis for small molecular regulation of ATXN1-CIC interaction. Subsequent validation involved functional blockade neural progenitor based SCA1 model, confirming the rescue of the associated phenotype. These results contribute to the identification and validation of a novel small molecule with potential therapeutic implications for SCA1 treatment.