Lignans are biologically active compounds widely distributed, recognized, and identified in seeds, fruits, and vegetables. Lignans have several intriguing bioactivities, including anti-inflammatory, antioxidant, and anticancer activities. Nrf2 controls the expression of many cytoprotective genes. Activation of Nrf2 is a promising therapeutic approach for treating and preventing diseases resulting from oxidative injury and inflammation. Lignans have been demonstrated to stimulate Nrf2 signaling in a variety of in vitro and experimental animal models. The review summarizes the findings of fourteen lignans (Schisandrin A, Schisandrin B, Schisandrian C, Magnolol, Honokiol, Sesamin, Sesamol, Sauchinone, Pinoresinol, Phyllanthin, Nectandrin B, Isoeucommin A, Arctigenin, Lariciresinol) as antioxidative and anti-inflammatory agents, affirming how Nrf2 activation affects their pharmacological effects. Therefore, lignans may offer therapeutic candidates for the treatment and prevention of various diseases and may contribute to the development of effective Nrf2 modulators.