Parkinson’s disease (PD) affects more than 6 million people worldwide, and will affect more in coming decades. There are no drugs available for PD that alter progression of disease. Current symptomatic treatments provide limited relief and have side effects. Enhanced GABAergic neurotransmission contributes to Parkinson’s disease (PD) pathogenesis and to some motor and non-motor symptoms. In animal models, GABA levels are increased in substantia nigra pars compacta, leading to reduced expression of tyrosine hydroxylase (TH) in neurons which contributes to the behavioural deficits. The aim was to evaluate whether treatment with golexanolone, a well-tolerated GABAA receptor-modulating steroid antagonist in clinical development, that reduces GABAA receptors activation and neuroinflammation, may improve some motor and non-motor deficits in a rat model of PD. We used the unilateral 6-OHDA rat model. Golexanolone treatment started four weeks after surgery. 6-OHDA rats showed impaired motor coordination and locomotor gait alterations which were improved by golexanolone treatment. 6-OHDA rats also showed non-motor deficits including increased fatigue, anxiety, anhedonia (a symptom of depression) and impaired short-term memory. These alterations were reversed by golexanolone treatment without inducing dyskinesia, as L-DOPA does. Golexanolone also reversed some neuroinflammation parameters such as activation of microglia and astrocytes. Golexanolone treatment reduces the decrease of tyrosine hydroxylase and prevented the increase of alpha-synuclein in striatum.Golexanolone treatment may be useful to improve different symptoms that affect the patients’ quality of life: fatigue, anxiety, depression, some aspects of motor coordination and locomotor gait, and some cognitive alterations