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<i>Kaempferia parviflora</i> Wall. ex Baker (KP) or “Kra-chai-dam” has been shown to exhibit several pharmacological effects including anti-inflammation, antimicrobial, and sexual-enhancing activity. The objectives of this study included an investigation of the effect of KP rhizome extract against glutamate-induced toxicity in mouse hippocampal HT-22 neuronal cells, determination of the underlying mechanism of neuroprotection, and an evaluation of the effect of KP extract on the longevity of <i>Caenorhabditis elegans</i>. HT-22 cells were co-treated with glutamate (5 mM) and KP extract (25, 50, and 75 μg/mL) for 14 h. Cell viability, intracellular reactive oxygen species (ROS) assay, fluorescence-activated cell sorting (FACS) analysis, and Western blotting were performed. The longevity effect of KP extract on <i>C. elegans</i> was studied by lifespan measurement. In HT-22 cells, co-treatment of glutamate with KP extract significantly inhibited glutamate-mediated cytotoxicity and decreased intracellular ROS production. Additionally, the glutamate-induced apoptosis and apoptotic-inducing factor (AIF) translocation were blocked by KP extract co-treatment. Western blot analysis also demonstrated that KP extract significantly diminished extracellular signal-regulated kinase (ERK) phosphorylation induced by glutamate, and brain-derived neurotrophic factor (BDNF) was recovered to the control. Moreover, this KP extract treatment prolonged the lifespan of <i>C. elegans</i>. Altogether, this study suggested that KP extract possesses both neuroprotective and longevity-inducing properties, thus serving as a promising candidate for development of innovative health products.