Piperine and capsaicin are important molecules with biological and pharmacological activities. This study aimed to evaluate the cytogenotoxic and protective effect of piperine and capsaicin on Allium cepa cells. A. cepa roots were exposed to negative (2% Dimethylsulfoxide) and positive (Methylmethanesulfonate, MMS, 10 µg/ mL) controls, and four concentrations (25-200 µM) of piperine or capsaicin (alone) or associated before, simultaneously or after with the MMS. Only the lowest concentration of piperine (25 µM) showed a protective effect because it was not genotoxic. Piperine and capsaicin were cytotoxic (50, 100 and 200 µM). Piperine (50 to 200 µM) caused a signifi cant increase in the total average of chromosomal alterations of in A. cepa cells.For capsaicin, the genotoxic effect was dose-dependent with a signifi cant increase for all concentrations, highlighting the signifi cant presence of micronuclei and nuclear buds for the two isolates. In general, bioactive compounds reduced the total average of chromosomal alterations against damage caused by MMS, mainly micronuclei and/or nuclear buds. Therefore, the two molecules were cytotoxic and genotoxic at the highest concentrations, and did not have cytoprotective action, and the lowest concentration of piperine demonstrated important chemopreventive activity.