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Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100 μM) protected cells from BPA (30 μM)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50 mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10 mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effects against BPA-induced oxidative stress. We observed that ALA significantly replenished the declined neurobehavioral and cognitive performances, decreased muscle coordination and alerted short-term recognition memory in mice exposed to BPA. Our results suggest that ALA has a promising role in modulating BPA-induced neurotoxicity in C8-D1A mouse astrocyte cells as well as neurochemical and neurobehavioral deficits in C57BL/6J male mice and its antioxidant and free radical scavenging activities may in part be responsible for such an effect. [ABSTRACT FROM AUTHOR]