Dengue viral infection was emerging as a most significant lethal disease, found it’s widespread pathogenesis against the mankind. The treatment and eradication of dengue viral infections becomes challenging since there is no vaccines and drugs to combat the disease. The proposed study is based on the In silico screening of fucoidan (sulfated polysaccharide) derived from brown seaweed Stoechospermum marginatum against Dengue Virus (DENV) 3L6P Non Structural proteins NS2B/NS3 Protease (NS2B/NS3 pro) of DENV-2 serotype. The conventional wet-lab on optimized fucoidan derivatives will serve as the ideal source of lead molecule in the treatment of dengue viral infections. Since there were no approved antiviral drugs or vaccines against DENV infection demands an extensive study. The current In silico molecular docking study stands useful for the design and development of novel drug fucoidan compound having better inhibitory activity against the dengue viral proteins 3L6P NS2B/NS3 Protease of DENV-2 strain. Aminated, sulfated, phosphorylated, and acetylated fucoidans were docked with the dengue viral protein (NS2B/NS3 Protease). The docking scores were highest for when amino fucoidans were docked against NS2B/NS3 Protease giving a docking score of -10.8 kcal/mol followed by Over sulfated fucoidan (-9.9 kcal/mol), and phosphorylated fucoidans (-8.913 kcal/mol). Among the docked proteins against fucoidan derivatives, acetyl fucoidans gave a minimum docking score of -6.2 kcal/mol), and unsubstituted fucoidan showed less binding affinity when compared with the fucoidan derivatives, which concludes that fucoidan controls NS2B/NS3 Protease expression. The fucoidan derivatives will be a potential drug candidate if further be validated by wet-lab studies for their proper function.