Colorectal cancer is one of the leading causes of death worldwide, and healthy diet is critical in preventing it. This study intends to investigate phenolic profile, antioxidant, and anti-proliferative activity as well as Glutathione S-transferase (GST) inhibition activity of water extract of Salvia fruticosa Mill. (SF.) HPLC analysis revealed that the main bioactive ingredients of SF were rosmarinic and caffeic acid. Total phenolic and flavonoid contents were 425.1mg GAE/g extract and 94.7mg CE/g extract, respectively. SF exhibited high antioxidant activity through DPPH and ABTS assays. The extract exhibited time and dose-dependent anti-proliferative activity on colorectal adenocarcinoma cell lines (Caco-2 and HT-29). The extract also inhibited GST activity in a mixed-type manner, with an IC50 value of 6.8 mu g/mL. To conclude, the results suggest that SF may be considered as a medicinal plant which can be used in theprevention and treatment of colon cancer, besides chemotherapy drugs.