Background: Catha edulis is an evergreen plant belonging to the Celastraceae family, used by the people of Africa, Yemen, and some part of Saudi Arabia as a recreational plant. They chew it alone or in combination with alcohol for attaining euphoria. Objective: There are contradictory studies in the genotoxic potential of the leaves of this plant. So far, the accomplished studies were conducted with much high doses. Hence, the current study has been designed to check the genotoxicity of khat-leaves extract with subcytotoxic concentration in human peripheral blood lymphocytes. Materials and Methods: We have employed comet assay, micronuclei (MN) analysis, and Ames test to evaluate the objectives. Results: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay has revealed that there is a dose-dependent reduction in cell viability with an IC50value of 76.5 μg/ml at 24-h treatment. The results of the comet assay have showed a nonsignificant difference between control and treatment up to 40 μg/ml extract. There was no dose-dependent increase in the frequency of binucleated cells with MN and reduction of cell proliferation in all the doses. The extract showed no mutagenic effect, in both TA98 and TA100 strains even with S9 activation. Conclusion: Under the experimental conditions employed in the present study, khat has been found to be nongenotoxic at subcytotoxic level. Abbreviations used: DMSO: Dimethyl sulfoxide; GIT: gastrointestinal tract; HPBL: Human peripheral blood lymphocytes; KCL: Potassium chloride; LCQ: Low-content quantification; MMC: Mitomycin C; RPMI: Roswell park memorial institute; SWGDRUG: Scientific working group for seized drugs.