<p>Stress granules (SGs) are membrane-less cytoplasmic assemblies composed of mRNAs and RNA-binding proteins (RBPs) that transiently form to cope with various cellular stressors by halting mRNA translation and, consequently, protein synthesis. SG formation plays a crucial role in regulating multiple cellular processes, including cellular senescence, inflammatory responses, and adaptation to oxidative stress under both physiological and pathological conditions. Dysregulation of SG assembly and disassembly has been implicated in the pathogenesis of various diseases, including cardiovascular diseases (CVDs), cancer, viral and bacterial infections, and degenerative diseases. In this review, we survey the key aspects of SGs biogenesis and biological functions, with a particular focus on their causal involvement in CVDs. Furthermore, we summarized several SG-modulating compounds and discussed the therapeutic potential of small molecules targeting SG-related diseases in clinical settings.</p> Graphical Abstract <p></p>