Phyllanthus emblica, a traditional Thai medicinal plant, was investigated for its chemopreventive potential through comprehensive phytochemical profiling and mechanistic evaluation of its dichloromethane extract (DCME) and silica gel column fractions (D1, D2, D3). Advanced LC-MS/MS analysis, coupled with HPLC, identified phenolic acids, flavonoids, and other bioactive compounds as major constituents, with D2 demonstrating selective enrichment in phenolic content and superior antioxidant capacity. DCME and D2 exhibited selective cytotoxicity against hepatocellular carcinoma HepG2 cells and colorectal cancer SW480 cells, while maintaining minimal toxicity to normal human fibroblasts MRC5 cells. Both extracts displayed significant antimutagenic activity against aflatoxin B1 and MeIQ-induced mutations in Salmonella typhimurium strains. Uniquely, fraction D1 induced NADPH:quinone oxidoreductase (NQO) activity, suggesting enhanced phase II detoxification pathway activation. DCME demonstrated superior overall bioactivity compared to individual fractions, likely attributable to synergistic interactions among its diverse phytochemical profile. These preliminary findings suggest the potential of P. emblica, particularly DCME and D2, as natural chemopreventive agents and provide mechanistic insights that warrant further in vivo validation and therapeutic exploration.