Berberis vulgaris L (B. vulgaris) and its main constituent berberine have been used in traditional medicine for a long time. This medicinal plant and berberine have many properties that have attracted the attention of researchers over the time. According to several studies, B. vulgaris and berberine exhibited anti-inflammatory, antioxidant, anticonvulsant, antidepressant, anti-Alzheimer, anti-cancer, anti-arrhythmic, antiviral, antibacterial and anti-diabetic effects in both in vitro and in vivo experiments. In regard to many reports on protective effects of B. vulgaris and berberine on natural and chemical toxins, in the current review article, the inhibitory effects of these compounds against natural, industrial, environmental and chemical toxicities with focus on cellular mechanism have been categorized. It has been mentioned that berberine could ameliorate toxicity of chemical toxins in brain, heart, kidney, liver and lung in part through antioxidant, anti-inflammatory, anti-apoptotic, modulation of mitogen-activated protein kinase (MAPK) and nuclear factor-ĸ B (NF-ĸ B) signaling pathways.