A MeOH extract from the whole plant Dendrobium venustum exhibited significant antimalarial and anti-herpetic activities. Bioassay-guided isolation of the plant extract resulted in the isolation of seven known phenolic compounds. Densiflorol B (3) and phoyunnanin E (6) showed the strongest antimalarial activity and a high selectivity index, whereas gigantol (2), batatasin III (5) and phoyunnanin C (7) exhibited moderate activity. Compounds 2 and 5 also showed weak activity against the Herpes simplex virus. This study is the first report on the chemical and biological activities of D. venustum.