It is well known that liver diseases are a major health problem and that there is a lack of hepatoprotective agents. Turnera diffusa (damiana) is a plant with a widespread distribution in México, which has many traditional uses, including the treatment of hepatic illnesses. Based on the bioassay-guided fractionation of a methanolic extract obtained from the aerial part of T. diffusa, we purified and identified a compound called hepatodamianol (1). This C-glycoside exhibited a four times greater hepatoprotective effect than the widely used hepatoprotective agent silibinin against carbon tetrachloride damage in an in vitro model using HepG2 cells. Hepatodamianol produced no cytotoxic effects and it exhibited a high antioxidant capacity. Therefore, hepatodamianol is a good candidate compound for testing as a hepatoprotective agent in a preclinical trial.