Sickle cell anemia (SCA) is a hereditary blood disorder characterized by abnormal hemoglobin production, leading to chronic hemolysis and episodic vaso-occlusive crises (VOCs). Pregnancy in women with SCA poses significant clinical challenges due to the increased physiological demands, which exacerbate hemolysis and increase maternal and fetal risks. This review explores the pathophysiology of hemolysis in SCA during pregnancy, its clinical implications, and management strategies aimed at improving maternal and fetal outcomes. Hemolysis can result in severe anemia, acute chest syndrome, increased risk of infections, and adverse fetal outcomes, such as intrauterine growth restriction and preterm delivery. Management strategies for hemolysis in pregnancy include blood transfusions, pharmacological therapies, nutritional supplementation, and emerging treatments like gene therapy. Blood transfusions are widely used to mitigate anemia and reduce the number of circulating sickled cells, while pharmacological agents such as L-glutamine help address oxidative stress. Nutritional support, particularly with folic acid and antioxidants, is essential in promoting healthy red blood cell production and mitigating oxidative damage. Emerging therapies like gene editing offer promising future directions for more effective management of SCA and pregnancy-related hemolysis.