Abstract Since the beginning of the 21st century, studies have focused on developing drugs from naturally occurring compounds. Berberine (Brb) as a plant‐derived compound is of interest. It is an isoquinone alkaloid which is derived from Berberis aristata, Berberis aquifolium and Berberis vulgaris. This plant‐derived compound has a variety of pharmacological effects such as antioxidant, anti‐inflammatory, antidiabetic, antidiarrheal, antitumor, antimicrobial, and anti‐inflammatory. Various studies have demonstrated the therapeutic and biological activities of Brb, but there is a lack of a precise review to manifest the signaling pathway of action of Brb. The nuclear factor erythroid 2‐related factor 2 (Nrf2) is a highly conserved pathway which mainly involves in preservation of redox balance. At the present review, we describe the therapeutic and biological activities of Brb as well as the relevant mechanisms specially focused on the Nrf2 signaling pathway.