Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is characterized by chronic nonspecific intestinal inflammation. Despite considerable efforts, IBD remains a heavy burden on society and human health, with increasing morbidity. Posttranslational modification, especially histone acetylation, is a key process in controlling DNA transcriptional activity. Histone deacetylases (HDACs) play a vital role in the mechanism of IBD pathogenesis through histone and nonhistone protein deacetylation. Herein, we present a summary of different categories of HDACs as well as HDAC inhibitors (HDACis) and analyze the role of HDAC inhibition in alleviating IBD along with its mechanism, as well as clinical potential of HDACis in IBD treatment.