Plectranthus madagascariensis is used as a traditional medicine in Southern Africa. In search of compounds and activities supporting the medicinal use, the chemical profile of the methanolic extract was studied by high-performance liquid chromatography with diode array detection (HPLC-DAD). Four major constituents were isolated and identified as rosmarinic acid (1), 7β,6β-dihydroxyroyleanone (2), 7β-acetoxy-6β-hydroxyroyleanone (3) and coleon U quinone (4). The two abietane diterpenoids (2 and 3) were isolated for the first time from this species. Antimicrobial, cholinesterase and α-glucosidase inhibitory activities of these compounds were studied. The compounds exhibited inhibitory activity on α-glucosidase with IC50 values from 33 to 275 μM. Abietanes showed potent antibacterial activity against Staphylococcus aureus and Enterococcus faecalis.