Eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are two biologically active omega-3 polyunsaturated fatty acids (n-3 PUFA), acquired by nutrition and incorporated in cell membranes’ phospholipids, thus playing a crucial role in human health and homeostasis. Due to their potential cardioprotective, anti-inflammatory, and anti-arrhythmic actions, n-3 PUFA emerge as an interesting therapeutic option for cardiac surgery (CS) patients. The aim of this review was to assess the effects of perioperative administration of n-3 PUFA in CS patients. A comprehensive literature search was conducted in order to identify prospective cohort studies and randomized controlled trials (RCT) reporting on the perioperative effects of n-3 PUFA among adult patients undergoing CS. A total of 31 articles, published between 1995 and 2022, including 10 543 patients, met the inclusion criteria. There seems to be a beneficial effect of n-3 PUFA supplementation for arrhythmias such as in Postoperative Atrial Fibrillation (POAF), reduction of Intensive Care Unit Length of Stay (ICULOS) & Hospital Length of Stay (HLOS), reduction in postoperative ventilation time, in inotropic demand, in postoperative fatigue, as well as in overall morbidity and mortality. Moreover, n-3 PUFA increase antioxidant potential, attenuate oxidative stress and inflammation with subsequent significant reduction in myocardial ischemia/reperfusion (I/R) injury, thus promoting early metabolic recovery of the heart after elective CS leading to improved myocardial protection. They represent a readily available and cost-effective strategy that could improve the outcome of patients undergoing CS, by reducing the risks of serious cardiovascular adverse events (AE), both peri- and post-operatively.