Background: Monosodium Glutamate (MSG) is one of the most commonly used flavors that may lend to motor incoordination. Alpha-lipoic acid (ALA) has antioxidant and anti-inflammatory effects with neuro-protective effects. Objectives: Present work aimed to elucidate possible protective potential of ALA on the motor incoordination induced by MSG and the possible underlying mechanisms. Materials and Methods: Seventy male Wister albino rats were randomized into five groups: 1-Control group (10 rats). 2-MSG group (20 rats): MSG 3 wks and MSG 6 wks ten rats each. 3-ALA pretreated group (10 rats). 4-ALA cotreated group (20 rats): ALA cotreated 3 wks and ALA cotreated 6 wks ten rats each. 5-Alpha-Lipoic acid-post-group. Thereafter, motor coordination assessed using Rotarod and Footprint analysis were assessed in addition to serum Malondialdehyde (MDA), total antioxidant capacity (TAC), Tumor necrosis factor-alpha (TNF-α), cerebellar brain derived neurotrophic factor (BDNF) and Oxidative DNA damage were measured. Also, histo-pathological examination of cerebellar tissue was performed and number of purkinjie cells was assessed. Results: ALA resulted in better improvement for MSG-induced motor incoordination, oxidative impairment and microscopic alterations of cerebellar architecture in cotreated group than that of post-treated group, with insignificant change in pretreated group. Conclusion: ALA exhibit protective effect against motor incoordination, oxidative stress and cerebellar damage induced by MSG toxicity best as cotreatment, less when used as post-treatment but this effect useless as pretreatment.