Tardive dyskinesia (TD) is a syndrome associated with administration of antipsychotics drugs and may be a consequence of a free radical increase. Ilex paraguariensis (IP), rich in polyphenols, is used to prepare a tea-like beverage, the "mate", and has been investigated for its antioxidant action. Here, we examined the aqueous extract of IP on in vitro TBARS production and in vivo study, using two behavioral models, i.e., haloperidol-induced orofacial dyskinesia (evaluated measuring vacuous chewing movements, VCMs) and memory dysfunction, evaluated in a water-maze task. In vitro, we examine different concentrations of IP against the basal, Fe(II) and sodium nitruproside-induced TBARS production in rat brain homogenate. IP extract was able to prevent the basal formation of TBARS (IC50 = 6.6 mg/ml) and TBARS induced by SNP (IC50 = 3.7 mg/ml) and Fe(II) (IC50= 4.8 mg/ml). Haloperidol administration (12 mg/kg/week, im, x4 weeks) increased VCMs (p <0.001). Rats treated with mate (50 g/l, ad libitum, 60 days) did not exhibit the increase in VCMs observed in control rats treated with haloperidol (p <0.001). In the water maze task, haloperidol treated animals displayed an impairment in memory acquisition (p <0.05) compared to rats treated with vehicle. The "mate" prevented the effects of haloperidol in this behavioral paradigm. Our results indicate that IP exhibits an antioxidant role probably related to the presence of polyphenols. The benefit of IP is possibly related to an indirect modulation of oxidative stress.