is study examines the inhibitory effects of the aqueous extract from guava twigs (GTE), Psidium guajava L., on mutation and oxidative damage. e results show that GTE inhibits the mutagenicity of 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen, and 2-aminoanthracene (2-AA), an indirect mutagen, toward Salmonella typhimurium TA 98 and TA 100. In addition, GTE shows radical scavenging, reducing activities, tyrosinase inhibition, and liposome protection effects. Meanwhile, GTE in the range of 0.1-0.4 mg/mL protects liver cells from tert-butyl-hydroperoxide-(t-BHP-) induced cytotoxicity. Furthermore, the cytotoxicity inhibition of GTE in the t-BHP-treated cells was demonstrated in a dose-dependent manner. High-performance liquid chromatography analysis suggests that the major phenolic constituents in GTE are gallic acid, ferulic acid, and myricetin. ese active phenolic components may contribute to the biological protective effects of GTE in different models. e data suggest that GTE exhibiting biological activities can be applied to antimutation, antityrosinase, and antioxidative damage.