Huntington's disease (HD) is an inherited, hyperkinetic condition manifested by a triad of motor abnormalities, progressive cognitive impairment, and psychiatric disturbances. Oxidative stress has been implicated among other cellular processes in the pathogenesis of HD. Arbutin, a hydroquinone antioxidant, is reportedly neuroprotective in several animal models of neurodegenerative diseases. Hence, this research aimed to investigate the neuroprotective effect of arbutin against HD using in silico, in vitro, and in vivo experimental approaches. Schrodinger software was used for the in-silico studies, while SH-SY5Y cells were used for in-vitro studies. In the in vivo studies, adult Wistar rats were divided into five groups and 3-nitro propionic acid (3-NPA) (10mg/kg/day,i.p) alone, and with arbutin (50 and 100mg/kg/day,i.p.) was administered for 21 days. The body weight and behavioural parameters, including locomotor activity and motor coordination, were assessed on the 1