Objective: To compare the antioxidant and anti-genotoxic properties of Alpinia (A.) galanga, Curcuma (C.) amada, and C. caesia. Methods: Cytotoxicity of ethanolic extracts of A. galanga, C. amada, and C. caesia at selected doses was evaluated by trypan blue, MTT, and flow cytometry-based assays. Genotoxicity and anti-genotoxicity (against methyl methanesulfonate, 35 μM and H2O2, 250 μM) of these plants were studied by comet assay in human lymphocytes in vitro. Furthermore, DPPH, ABTS, FRAP, lipid peroxidation, and hydroxyl radical scavenging assays were performed to study the antioxidant potentials of the plants. Finally, anti-genotoxic potential of C. amada was validated in Swiss albino mice using comet assay. Phytochemical composition of C. amada was determined by GC/MS and HPLC. Results: The selected doses (2.5, 5, and 10 μg/mL) of A. galanga, C. amada, and C. caesia were non-toxic by cytotoxicity tests. All three ethanolic extracts of plant rhizomes demonstrated antioxidant and anti-genotoxic properties against methyl methanesulfonateand H2O2-induced oxidative stress in human peripheral blood lymphocytes in vitro. Multivariate analysis revealed that various antioxidant properties of these extracts in DPPH, ABTS, and FRAP assays were strongly correlated with their total phenolic constituents. C. amada extract conferred protection against cyclophosphamideinduced DNA damage in the bone marrow cells of mice and DNA damage was significantly inhibited by 2.5 mg/kg C. amada extract. Conclusions: C. amada is rich in potentially bioactive molecules and exhibits potent antioxidant activities. Its anti-genotoxicity against cyclophosphamide-induced oxidative stress is also confirmed in this study.