The liver is an organ with several important biofunctions, for which there are very few effective and safe preparations that promote the functioning, protection, and regeneration of cells. Sufficiently safe preparations with hepatoprotective activity can be found in plants. The aim of our study was to investigate the chemical composition of an extract made from American cranberry (Oxycoccus macrocarpus(Ait.) Pursh) leaves and its amino-acids preparations as well as their possible hepatoprotective activity. Using the UPLC-MS/MS method, we identified 19 phenolic compounds (8 flavonoids (flavones and flavonols), 4 anthocyanins, 3 hydroxycinnamic acids, and 2 catechins). The prophylactic and therapeutic administration of the American cranberry-leaves extracts led to a decrease in the lipid-peroxidation process during a study of tetrachloromethane acute toxic damage in the liver of rats. As a result of animal studies, the most effective hepatoprotective activity was found in the extract preparations with valine and arginine.