Abstract: Histone deacetylase 9 (HDAC9), a member of the class IIa histone deacetylase family, has attracted considerable attention in recent years because of its involvement in the development and progression of cardiovascular diseases. To provide a comprehensive understanding of the cardiovascular regulatory functions and therapeutic potential of HDAC9, this review focuses on three aspects: its biological characteristics, roles in cardiovascular diseases, and targeted interventions. First, the protein structure, splice variants, transcriptional regulation, and nucleocytoplasmic shuttling of HDAC9 are described. Then, research advances concerning its roles in atherosclerosis, heart failure, myocardial infarction, and aortic aneurysm/dissection are reviewed, with particular emphasis on its interactions with transcription factors, inflammatory signaling pathways, and noncoding RNAs. Finally, the major structural classes and structure–activity relationships of HDAC9 inhibitors are summarized, together with emerging intervention strategies such as RNA interference and targeted protein degradation. This review may provide a basis for elucidating the mechanisms underlying HDAC9-related cardiovascular diseases and developing selective HDAC9-targeted therapies.