Molasses, the main byproduct of sugar production, is a well-known source of antioxidants. In this study sugar cane molasses (SCM) and sugar beet molasses (SBM) were investigated for their phenolic profile and in vitro antioxidant capacity and for their protective effect in human HepG2 cells submitted to oxidative stress. According to its higher phenolic concentration and antioxidant capacity in vitro, SCM exhibited an effective protection in cells, comparable to or even greater than that of α-tocopherol. Data herein reported emphasize the potential health effects of molasses and the possibility of using byproducts for their antioxidant activity. This is particularly important for consumers in developing countries, as it highlights the importance of consuming a low-price, yet very nutritious, commodity.