Dengue fever is a rapidly spreading infection that affects people all over the tropics and subtropics, posing a significant public health threat. The brown seaweed Stoechospermum marginatum was found all over the world, from South Africa (Indian Ocean) to Australia (Pacific Ocean), among other places. In India, it is only available along the coast of the Bay of Bengal, which is a small region. Various metal oxides were proved to be successful in the formation of nanoparticles and zinc is one among them. In this present study, an attempt was made to study the anti-dengue activity of green synthesized zinc oxide nanoparticles of crude fucoidan isolated from brown seaweed S. marginatum. The fucoidan was isolated from the seaweed by acid extraction method and then characterized by UV, HPLC, and Fourier Transform Infra-Red (FT-IR) Spectroscopy. Then it was biosynthesized into ZnO nanoparticles and characterized by SEM-EDAX analysis. The results showed the formation of fucoidans and SEM studies showed the crystalline nature of the synthesized nanoparticles. The size of nanoparticles was in the range of 80–126 nm. The synthesized nanoparticles were tested with the C6/36 cell line and it was shown 99.09% of anti-dengue activity against the tested cell line. As an antiviral agent, the ZnO nanoparticles of fucoidans have been shown to be an excellent lead molecule for the treatment of dengue fever. © 2023 Elsevier B.V., All rights reserved.