Context: Dendrobium longicornu is a traditional medicinal plant widely used in Asia. It has many bioactive compounds like bibenzyl, phenanthrenes, phenolic compounds. There has been little research in the cytotoxic and antioxidant effects of D. longicornu. Aims: The aim of this study was to investigate the cytotoxic and antioxidant activities of this plant. Settings and Design: Antioxidant and cytotoxic activity of Dendrobium longicornu extracts. Methods and Material: The plant extracts were prepared by soxhlet’s extractor in organic solvents, acetone and ethanol. The total polyphenol content (TPC) in the extracts was determined spectrophotometrically by the Folin-Ciocalteu method and the total flavonoid content (TFC) by aluminium chloride method. The antioxidant activity was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl) method. The cytotoxic activity was evaluated against human brain tumor cells (U251) and cervical cancer cells (HeLa) using MTT assay. Statistical analysis used: Regression analysis was done for calculation of IC50. Duncan multiple range test and Dunnett test were done to compare the data. Results: The Dendrobium longicornu acetonic extract (DLA) showed significantly highest TPC and TFC than Dendrobium longicornu ethanolic extract (DLE). The antioxidant activity was also significantly higher in DLA followed by DLE. Highest cytotoxicity (i.e., lowest IC50 value) was found for the DLA on U251 cells and DLE on HeLa cells. Conclusions: This result concluded that D. longicornu is a potential source of antioxidant and cytotoxic agents.