HDAC8-selective inhibitors not only explore the biological functions of HDAC8 but also proved to be immensely significant anticancer agents with few side effects. Of the several classifications, hydroxamic acid-based HDAC inhibitors proved that they produce therapeutic potential against cutaneous T-cell lymphomas (CTCL). By considering the skeleton of the hydrophobic pocket of HDAC8 and its catalytic site, about 52 chiral heterocyclic hydroxamic acid derivatives were designed as inhibitors using structure based drug design approach. Herein, we generated common feature pharmacophore for mapping the designed ligands. Furthermore, these ligands were subjected to docking by C DOCKER method and the binding energy was calculated. In addition, toxicity was predicted using ADMET and TOPKAT simulations. Finally, by combining the results of the above studies, compounds with good binding energy and less toxicity were considered as the best inhibitors. However, five compounds CMP 9, 25, 26, 33 and 38 successfully satisfied all the studies among the 52 compounds screened and appeared to be a promising potent inhibitors against HDAC8.