Using Schrodinger 2021-3, in silico molecular docking and ADMET investigations of the proposed compounds were carried out upon the binding cavity standardized for Legumain. In order to analyses the newly synthesized benzotriazole (6a–p) mannich base derivatives, 1HNMR, 13CNMR, and mass spectrum data were collected. These substances (6a-p) were tested for their anticancer properties on four different human cancer cell lines using the MTT method. The test compounds' binding to the legumain binding site has been confirmed by the IFD results, which concur with those of XP docking experiments. Compounds' anticipated ADMET characteristics are within acceptable bounds. As compared to the control medication, the majority of the compounds showed excellent to moderate anticancer activity. Positive control values ranged from 0.13 0.017 to 3.08 0.135 M, and the drugs' IC50 values ranged from 0.012 0.001 to 22.9 9.11 M. These 6a, 6c, 6e, 6f, 6j, 6n, and 6p were shown to have more powerful anticancer properties than etoposide among synthetic chemicals. The chemical 6a, which has an electron-donor (3,5-dimethoxy) group on the phenyl ring, had the most anticancer effects when tested against four cancer cell lines, with IC50 values of MCF-7 = 0.012 0.001, A549 = 0.18 0.076, Colo-205 = 0.34 0.083, and A2780 = 0.07 0.006 M, respectively.