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Zingiber officinale is a type of Ginger with antioxidant activity. Its use is described in cellular models such as pancreatic and intestinal cancer cell lines. However, the biochemical bases of antitumor, anti-inflammatory and antioxidant activities have not yet been fully elucidated. The aim of this study was to evaluate in H2O2-induced oxidative stress the effect of ginger extract (GE) on HT1080 cell viability, ROS production, AKT activation, and mitochondrial membrane potential. Results revealed a significant cell viability decrease at increasing GE concentrations; at 200 and 400 µg/ml GE resulted in decreased ROS production; at 200 µg/ml produced a significant increase in mitochondrial membrane potential, but no difference was observed with GE at 400 µg/ml. In untreated cells basal AKT activation was not observed. Conversely, treatment with 750 uM H2O2 led to Ser473 phosphorylation. Additionally, treatment with GE at 200 µg/ml decreased AKT activation. Reports describe GE biological activities; none the less, novel approaches to investigate intracellular changes are described in this study. In conclusion, this study characterized GE induced intracellular changes, leading to changes in mitochondrial membrane potential and signaling protein levels as AKT, reducing cell viability