The present study has been designed to investigate the antioxidant and antimutagenic potential of hydrolyzed and non-hydrolyzed extracts of twenty medicinal plants belonging to different plant families like Amaranthaceae, Cucurbitaceae, Labiatae, Fabaceae, Solanaceae, Poaceae, Malvaceae and Zygophyllaceae. Hydrolyzed extraction was carried out using acidified methanol and non-hydrolyzed extracts were obtained with aqueous methanol. Both types of extracts were evaluated for phenolic contents, antioxidant, mutagenic and antimutagenic potential and genoprotective activity. Hydrolyzed extracts of all plants represented higher phenolic contents, antioxidant and antimutagenic potential as compared to non-hydrolyzed extracts. Mentha longifolia (402.8±1.9 mg GAE/g dry extract), Citrullus colocynthus (396.4±1.9 mg GAE/g dry extract) and Mimordica dioca (354.4±1.9 mg GAE/g dry extract) showed highest phenolic contents. Cassia angustifolia (230.4±2.6 mg AAE/g dry extract), Mimordica dioca (132.6±0.8 mg AAE/g dry extract) and Mentha longifolia (131.7±1.5 mg AAE/g dry extract) presented largest reducing power in terms of ascorbic acid equivalents (AAE). Highest free radical scavenging was shown by Citrullus colocynthus (96.21±1.0%; IC50 2.11±0.12 µg/mL), Achyranthus aspera (93.1±0.4%; IC50 6.5±0.10 µg/mL), Mentha longifolia (92.4±1.0%; IC50 14.3±0.1 µg/mL). Citrullus colocynthus (96.21±1.0%; IC50 2.11±0.12 µg/mL), Mimordica dioca (91.91±1.0%; IC50 17.22±0.36 µg/mL) and Mentha longifolia (92.4±1.0%; IC50 14.3±0.1 µg/mL) exhibited highest antioxidant activity in terms of inhibition to lipid peroxidation. Lowest cytotoxicity was observed for Citrullus colocynthus (2.65±0.09%), Achyranthus aspera (2.95±0.14%) and Mentha longifolia (3.95±0.08%) by evaluating haemolytic activity. Highest antimutagenic potential was calculated for hydrolyzed extracts of Citrullus colocynthus (75.79±0.69%), Mimordica dioca (73.02±1.37%) and Achyranthus aspera (72.22±0.69%). Also, Citrullus colocynthus, Mimordica dioca and Achyranthus aspera showed considerable protection against oxidatively damaged DNA plasmid i.e. pBR322. Finally, it has been concluded that Citrullus colocynthus, Mentha longifolia, Mimordica dioca and Achyranthus aspera were the most bioactive plants of all selected medicinal plants as represented by the results of LCMS analysis that exhibited the presence of high concentrations of bioactive compounds in the extracts of these plants.…………………………………