According to the archaic Chinese prescription, Graptopetalum paraguayense E. Walther is used for medication purpose; however, no literature on its biophysical functions is presently available. This study was aimed to evaluate the antimutagenicity activities of water (GWE), 50% ethanolic (GE50), and 95% ethanolic (GE95) extracts of Graptopetalum paraguayense. The mutagenic and antimutagenic properties of the three extracts were investigated using Ames test. The results showed that all the extracts had no-mutagenicity effect toward all tester strains (Salmonella typhimurium TA97, TA98, TA100, TA102, and TA1535). All tested extracts had marked 100% inhibition effect against the mutagenicity of the diagnostic mutagens, 2-aminofluorene (2-AF) and 2-aminoanthracene (2-AA), in all tester strains with the S9 mix system.