Abstract Objectives Aloysia gratissima aqueous extract (AE) was investigated as a putative protective agent against quinolinic acid (QA)-induced seizures in mice and hippocampal cell damage. Additionally, AE and ferulic acid (FA), the major compound of AE, were tested against neurotoxicity evoked by glutamate or its N-methyl-D-aspartate receptor (NMDAR) agonist, QA on hippocampal slices, in vitro. Methods Mice were treated with AE before QA infusion (36.8 nmol/site) and seizures were analysed. Cellular viability and modulation of excitatory amino acid transport were verified in hippocampal slices. In-vitro AE or FA was tested against neurotoxicity induced by glutamate or QA. Key findings AE did not prevent QA-induced seizures; however, it prevented cellular death and disruption of excitatory amino acid transport. In-vitro AE (0.1 or 1.0 mg/ml) or FA (1 or 10 μm), improved cell viability against citotoxicity exerted by glutamate or QA, respectively. Both AE and FA have protective effects depending on activation of the phosphatidylinositol-3 kinase (PI3K) signalling pathway. Conclusions AE attenuated QA-induced cell damage possibly involving the glutamate transport modulation through NMDAR interaction. FA shows a similar profile of neuroprotection promoted by AE. Therefore, AE treatment might be a useful strategy in preventing brain damage caused by exacerbation of glutamatergic toxicity in nervous system disorders.