Our health and wealth are highly influenced by a number of viruses. Dengue is one of them having a global influence in absence of vaccines and antiviral. WHO suggested that the morbidity of dengue is increasing more than 6 times from 0.5 million in 2010 to over 3.34 million in 2016, following a sharp increase in 2019. The aim of the present study is to check the in vitro and in silico antidengue activity of Cyamopsis tetragonoloba supercritical extract in cell lines. The optimum yield of supercritical extract was obtained 0.13 g/10 g (1.3% w/w) at 40°C temp and 15 MPa pressure and further characterized by GC-MS. The antiviral assay was performed on C6/36 cell lines with 100 copies of dengue-2 virus and maximum nontoxic dose (31.25 lg/ml) of supercritical extract and their effect was detected by real-time RT-PCR. This study revealed that C. tetragonoloba supercritical extract inhibited the dengue-2 virus (99.9%). GC-MS analysis of C. tetragonoloba supercritical extract showed the presence of 10 compounds. The major compounds identified were Hexadecanoic acid, 15-methyl-methyl ester (24.498%); 9,12-octadecadienoyl chloride, (z,z)-(23.718%); methyl dodecanoic acid (13.228%); methyl-stearate (8.696%); Tridecanoic acid, 12-methyl-, methyl-ester (8.426%), dodecanoic acid (6.102%). The study reveals that C. tetragonoloba can be exploited to develop an effective, inexpensive, and specific anti-dengue. The molecular docking study demonstrated the binding energy of 1,2benzenedicarboxylic acid, bis(2-methylpropyl) ester (-4.1 kcal/mol), 9,12-octadecadienoyl chloride (z,z) (-4.0 kcal/mol) ligands were higher than others. It is concluded that C. tetragonoloba can play a major role to inhibit dengue-2 virus.