In the present investigation, methanolic extracts from shoots and roots of Tunisian Nigella sativa were assayed for their antioxidant and antimutagenic activities. The phenolic composition of the methanolic extracts was determined by RP-HPLC. The predominant phenolic compound was vanillic acid with a mean concentration of 143.21 and 89.94 mg per 100 g dry weight of shoots and roots, respectively. Shoots and roots showed comparable and strong superoxide scavenger activity; however, shoots exhibited higher DPPH radical scavenging, reducing and chelating activities than roots. Mutagenic and antimutagenic activities were determined by using the Ames test. Shoots and roots demonstrated important antimutagenic effects. Roots exhibited stronger activity than shoots with an inhibition percentage of 71.32%.