Purpose of review <p>This review explores the burgeoning frontier of the interplay between omega-3 fatty acids and the gut microbiome in cardiovascular disease (CVD) prevention. The sources, types, and biological effects of omega-3 fatty acids are examined, alongside the composition, function, and cardiovascular implications of the gut microbiome.</p> Recent findings <p>Cardiovascular disease remains a leading cause of mortality globally, necessitating novel preventative strategies. Omega-3 fatty acids, known for their anti-inflammatory and lipid-lowering properties, have been widely studied for their cardiovascular benefits. Concurrently, the gut microbiome has emerged as a crucial player in health and disease, including CVD. Recent studies have highlighted the influence of omega-3 fatty acids on gut microbiome composition and diversity, and conversely, the gut microbiome's impact on the metabolism and efficacy of omega-3&#xa0;s.</p> Summary <p>Clinical trials and observational studies highlighting the impact of omega-3 supplementation on gut microbiome and cardiovascular health are discussed, underscoring existing research gaps. Finally, this review concludes the potential for personalized approaches and future research directions to leverage the gut microbiome to enhance the cardiovascular benefits of omega-3 fatty acids are considered.</p> Graphical Abstract <p></p>