Arsenic is a highly menacing environmental pollutant that substantially affects the quality of life, even in traces. It develops various diseases through increasing intracellular ROS that interacts with vital organs. Chelation therapy is currently recommended for arsenic toxicity. However, these treatment options are not specific and only target symptoms. Besides, they also show toxic effects and irreversibly damage crucial organs. Hence, there is an urgent need for a potential and safer therapeutic strategy that can prevent arsenic toxicity. Therefore, in this study, we have investigated SA and EC individually and in combination against arsenic toxicity in HCT-116 cells. The results obtained from various experiments revealed that both plant materials comparably inhibited arsenic-induced cellular damage by increasing the antioxidant function. Conversely, combining both plants showed even better cytoprotection against arsenic toxicity. The FT-IR and HPLC analysis of the active fractions revealed the presence of polyphenol compounds (ferulic acid and gallic acid) responsible for the pharmacological effect. This finding is unique because no cytoprotective impact has been reported yet on this combination.