Diabetes is a group of global epidemic diseases with high prevalence and morbidity. The pathophysiological changes of diabetes can be affected by genes, environmental factors, and several socioeconomic factors. Histone post-translational modification is the central epigenetic mechanism regulated by genetic and environmental factors. Histone methylation and acetylation have been thoroughly studied in various pathological processes of diabetes, such as the metabolic memory phenomenon, inflammation, and endothelial dysfunction. In recent years, an increasing number of novel histone acylation modifications have been identified by mass spectrometry. The level of any novel histone modification depends on the relative concentration of its respective acyl-CoA, which can be generated through various intermediate metabolic pathways. Although studies have shown that these novel modifications and metabolic regulation of histone acylation have a close connection with diabetes, investigations on this connection have lagged. Moreover, the locations of acylation modification sites and how enzymatic reactions regulate diabetes and its complications remain largely unknown. This review summarizes the relationship between novel histone modifications and diabetes, mainly focusing on β-hydroxybutyrylation, propionylation, butyrylation, malonylation, and succinylation. We aim to highlight the typical characteristics of novel acylation modifications and provide a new perspective for further research on the pathogenesis and treatment of diabetes and its complications.