Among different Histone deacetylases (HDACs), histone deacetylase 3 (HDAC3) is an epigenetic drug target which is currently marked as a potential therapeutic strategy to combat various cancers. HDAC3 inhibitors are effective for the treatment of cancers, different neurodegenerative disorders, diabetes mellitus, cardiac diseases, HIV, inflammatory diseases, rheumatoid arthritis (RA), etc. Inhibition of HDAC3 metalloenzyme is a dynamic approach for drug design and discovery. This approach has gained considerable interest in recent years. The development of an effective therapeutic agent against HDAC3 is still challenging. A lot of work is still in demand. This current communication is a part of our extended work on HDAC3 inhibitors to achieve deep insight of knowledge about the structural information of HDAC3 inhibitors. This article is unique in terms of detailed structure-activity relationships (SARs) analysis. This may help to find out some important clues to design better active HDAC3 inhibitors in the future.Copyright © 2020 Elsevier Masson SAS. All rights reserved.