Salacia grandifolia is naturally found in the Atlantic Forest regions of Brazil. Despite the pharmacological potential of plants from the Salacia genus, phytochemical studies on this species have not been reported in literature. A new triterpene, 28hydroxyfriedelane-3,15-dione (1), and seven known compounds (friedelan-3-one (2), friedelan-3β-ol (3), friedelane-3,15-dione (4), 15α-hydroxyfriedelan-3-one (5), 28-hydroxyfriedelan-3-one (6), 30hydroxyfriedelan-3-one ( 7), and 29-hydroxyfriedelan-3-one ( 8)) were obtained from the hexane extract of Salacia grandifolia leaves. These isolated compounds and three extracts, hexane (EH), chloroform (EC), and ethyl acetate (EAE), were assessed for their potential biological activities, which consisted in the evaluation of antiviral activity against a murine coronavirus, mouse hepatitis virus 3 (MHV-3), antibacterial activity against the susceptible and methicillin-resistant Staphylococcus aureus (MRSA), and antileukemia activity against the THP-1 and K-562 cell lines. The extracts EH and EAE along with the triterpenes 1 and 6 exhibited moderate to high antiviral activity, with emphasis on 6, which presented an EC 50 value of 2.9 ± 0.3 μM. None of the compounds presented antibacterial activity against the tested strains. The evaluated compounds 1, 4, 6 and 7 exhibited low cytotoxic activity against the tested leukemia cell lines. Taken together, this study comprises an overview for the potential of the Salacia grandifolia biological activities, including a new isolated triterpene.