Sansevieria trifasciata Prain. and Sansevieria suffruticosa N.E.Br. were selected to evaluate their cytotoxic activity against colon (CACO2), lung (A-549) and liver (HepG-2) carcinoma cell lines. Results indicated that S. suffruticosa N.E.Br. showed a significant cytotoxic effect on CACO2 with IC50= 30.9 ± 0.72 μg/ml. Evaluating the phenolic and flavonoid contents, S. suffruticosa N.E.Br. has higher total phenolic and flavonoid contents than S. trifasciata Prain. The phenolic content was estimated using HPLC detecting the presence of apigenin-7-glucoside and cinnamic acid only in S. suffruticosa N.E.Br. with p-hydroxybenzoic acid and p-coumaric acid being the major compounds. While, catechin and kaempferol are the major compounds detected in S. trifasciata Prain. Phytochemical investigation of ethyl acetate fractions of both species results in isolation of chlorogenic acid, kaempferol, quercetin, and catechin from S. trifasciata Prain. and apigenin-7-glucoside and rutin from S. suffruticosa N.E.Br. Isolated compounds are identified using recent spectroscopic methods. All compounds are isolated for the first time from these species. Metabolomic profiling indicates the presence of phenolic acids, flavonoids and saponins in the alcoholic extracts of the two species. In addition, molecular docking study was done for further investigation of the possible targets involved in the cytotoxicity of the alcoholic extracts of the two Sansevieria species. The ability of some phenolic compounds to interact with EGFR cancer target site rationalizes the cytotoxic activity of S. suffruticosa N.E.Br. alcoholic extract as proven by their docking pattern and docking score.