Background: Mangrove plants have high potential in medical research and they have been used in traditional medicine for any diseases. Squalene, a natural 30-carbon triterpenoid compound, was originally obtained from Shark and for the first time isolated from mangrove plant species. From the historical background, it was known that squalene display protective actions against several diseases and carcinogens. Objective: Herein, we desire to report the in vitro evaluation of squalene on AGS cell line. In the present investigation, after 24 h incubation, the inhibitory effect of squalene was found to have significant activity on AGS cell lines proliferation. Materials and Methods: Mangrove plant isolated squalene compound was treated with gastric adenocarcinoma cancer cell line AGS for 24 h with control. The cells were treated at varying concentration range 10, 30, and 50 μg/mL. The cytotoxicity effect of squalene was studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide, mitochondria membrane potential, etc., Results: Among the tested concentrations, squalene at 50 μg/mL showed a higher level of mitochondrial depolarization, DNA fragmentation, and induced apoptosis in AGS cells when compared to control. A similar but lower activity was observed in minimum doses of 20 and 30 μg/mL compared to maximum dose of 50 μg/mL. A 50% and 100% cell viability was observed at 30 and 50 μg/mL, respectively. Likewise, there was a significant reduction in thiobarbituric acid reactive substrate and lipid hydroperoxides levels, while antioxidant enzymes like superoxide dismutase. Catalase, glutathione (GSH) peroxidase, reduced GSH, Vitamin-C (Vit-C), and Vitamin-E were increased on squalene treatment in a dose-dependent manner. Conclusion: On the basis of results, it was concluded that isolated compound (squalene) from Rhizophora mucronata had a potent antigastric carcinogenic effect at 50 μg/mL in AGS cell lines and appeared to be more sensitive toward the AGS cell line.