Sickle cell disease (SCD) is a genetic disorder caused by mutations in the β-globin gene, leading to the production of abnormal hemoglobin S (HbS). This results in rigid, sickle-shaped red blood cells that cause vaso-occlusive crises, chronic hemolysis, and multi-organ damage. Antibodies targeting SCD-related pathways have emerged as therapeutic and diagnostic tools. For instance, monoclonal antibodies like crizanlizumab (anti-P-selectin) reduce vaso-occlusion by inhibiting cell adhesion, while others target inflammatory cytokines (e.g., IL-1β, IL-6) to mitigate inflammation. Additionally, antibodies against complement proteins (e.g., C5) are explored to address hemolysis. Diagnostic antibodies detect biomarkers like fetal hemoglobin (HbF) or adhesion molecules to monitor disease progression or therapeutic response. Research also focuses on antibody-based strategies to enhance HbF production or block HbS polymerization. Despite challenges in specificity and immune-related risks, antibody therapies offer precision in modulating SCD pathophysiology, complementing traditional treatments like hydroxyurea or blood transfusions. Ongoing clinical trials aim to optimize efficacy and safety, highlighting their potential as transformative tools in SCD management.