Dendrophthoe falcata (L.f.) Ettingsh (Loranthaceae family) is a hemiparasite which has many medicinal applications and grows on a variety of hosts. Bioactivity of the hemiparasite shows a great host dependence, where it contains high antioxidant activity coupled with high toxicity when grown on the host Limonia acidissima. This study aimed to investigate the impact of environmental conditions on the bioactivity of the hemiparasite grown on L. acidissima (Rutaceae family), as the environmental stress may play a determining role in the production of secondary metabolites in a plant. The hemiparasite grown in Hambantota (Hamb -dry zone), Kurunegala (Kuru -intermediate zone) and Ambalantota (Amba -dry zone), were selected for this study. Sequential extracts by Soxhlet method from hexane (HE), ethyl acetate (EAE) and methanol (ME) were compared for antioxidant activity, polyphenolic content, toxicity and alkaloid content determined by DPPH, Folin-Ciocalteu, brine shrimp lethality and acid-base assays respectively. Antioxidant activity was approximately 40% higher for Kuru-ME compared to Hamb-ME and Amba-ME. A significant 180 -200% higher polyphenolic content was observed for Hamb-ME compared to the Amba-ME and Kuru-ME. Toxicity studies revealed that Hamb-EAE is 43% and 29% more toxic than Kuru-EAE and Amba-EAE. The alkaloid content of Hamb-ME showed the highest percentage with a less significant difference between the extracts of other two locations. On average, among the three locations, extracts of Kurunegala, Ambalantota and Hambantota showed the least, intermediate and highest bioactivities respectively experiencing the least, intermediate and most environmental stressed conditions. Hence, it can be concluded that the bioactivity is influenced by the environmental stress due to the impact of governing the secondary metabolites produced by Dendrophthoe falcata.