Ilex kudingcha C.J. Tseng is a nootropic used throughout Asia that shares a number of metabolites with Ilex paraguariensis used throughout South America. Our previous study using a Drosophila melanogaster rugose model of autism spectrum disorders (ASD) showed that consumption of an Ilex kudingcha extract (IKE) mitigates phenotypic characteristics of ASD and in normal mice, alters gene expression involved in cognition, metabolism, and protein synthesis. This study investigated the effects of IKE on prenatal sodium valproate (VPA) treatment-induced ASD core behavioral deficits and ASD associated behaviors, neurochemical markers and histological changes. IKE administration significantly mitigated these behavioral deficits and damaged Purkinje cells, PTEN expression and oxidative stress and resembled treatment with methylphenidate in its effect upon social behavior. These findings extend our previous study with D. melanogaster and together, indicate that IKE consumption ameliorates ASD-like properties in two animal models of ASD with different etiologies. Potential mechanisms involve reduction of oxidative stress, increased PTEN expression and cerebral Purkinje cell health. These data support further studies of IKE and related species for treatment of ASD.