Premna esculenta is an important medicinal plant which have been traditionally used by tribal people of Chittagong Hill Tracts of Bangladesh in the treatment of gout, arthritis, wound healing, cold, cough, headache, jaundice, lipoma, edema etc. Although the plant have various ethnopharmacological uses, it yet have not been undergone any chemical or pharmacological investigation. The study revealed that the ethanolic extracts of leaves possesses significant anti-inflammatory, anti-hyperlipidemic, hepatoprotective, CNS depressant & anti-oxidant activities while the ethanolic extract of roots showed significant anti-nociceptive activity. The ethanolic extract of the root exhibited strong in-vitro thrombolytic activity on human blood. These findings show that the plant have potential therapeutic efficacy and may serve as potential source of drug candidate. The work described in this study may be helpful for the bioactivity guided phytochemical analysis of the plant extracts to identify the potential lead compounds for the treatment of hyperlipidemic, cardiovascular, liver, painful and inflammatory disorders.