E Se tea, prepared from the leaves of Malus toringoides (Rehd.) Hughes, is a traditional beverage, but there is little known about its chemical substances. This paper is aimed to investigate the chemical composition, antioxidant, and cytoprotective activities of the extract and fractions from E Se tea. Sixteen compounds were characterized by UHPLC-ESI-HRMS/MS. Phloridzin was the main compound, especially in ethyl acetate fraction (EAF). Moreover, EAF had the highest total phenolic and flavonoid contents with 197.54 ± 7.52 mg gallic acid equivalents/g extract and 85.94 ± 5.39 mg rutin equivalents/g extract, respectively, and exhibited the strongest antioxidant capacity (DPPH: IC = 54.91 ± 3.38 μg/mL; ABTS: IC = 98.08 ± 6.92 μg/mL). Different fractions of E Se tea, especially EAF, significantly inhibited intracellular ROS generation, reduced cell apoptosis, and decreased oxidative stress damage in HO-induced HepG-2 cells. Therefore, the obtained results highlight that E Se tea is a promising source for functional beverage or nutritional foods.