Objective: To evaluate the antioxidant, anti-inflammatory and antiproliferative activities of the leaf extracts of Excoecaria agallocha L. Methods: To estimate the antioxidant effect of the extract from Excoecaria agallocha, various assays were carried out. Estimation of total phenolics was done by Folin–Ciocalteu micro-method, total antioxidant capacity was determined by sulphuric acid-ammonium molybdate method, reducing power assay was carried out by FRAP (Ferric cyanide (Fe3+) Reducing Antioxidant Power) assay method and free radical-scavenging activity was estimated by DPPH (diphenyl-picrylhydrazine) and ABTS methods. Bovine serum denaturation inhibition assay was performed to test the in vitro anti-inflammatory activity of the extract, MTT assay was carried out to find out the antiproliferative effect of the extract against SKMEL 28 skin cancer cell lines. The crude ethyl acetate fraction was finally analyzed by thin layer chromatography to reveal 8 bands indicating presence of various compounds that probably contributed to the various biological activities. Results: The total antioxidant activity, total phenolics content and reducing power assay tested with various solvent fractions of Excoecaria agallocha leaf extract showed that ethyl acetate fraction had the highest antioxidant activity, reducing power and phenolics content among other fractions. The scavenging effect of extracts and standards on ABTS•+decreased in the order: ethyl acetate>n butanol>water>petroleum ether>gallic acid. The relative percentage of inhibition of BSA denaturation by the ethyl acetate extract was found to be 85.38% at a concentration of 100 μg/ml in comparison to the standard diclofenac sodium which brought about 13.65% of inhibition of BSA denaturation at the same concentration. The GI50 was found to be 19.02 μg/ml for DMSO and 39.2 μg/ml for ethyl acetate fraction against SKMEL 28 skin cancer cell lines. Conclusion: These results suggest that the extracts of Excoecaria agallocha possess significant antioxidant, anti-inflammatory and antiproliferative activities. © 2014 All Rights Reserved.