Sickle cell disease, the most common genetic disease in the world, is a chronic hemolytic disease that can be complicated by severe vaso-occlusive pain crises resulting in tissue necrosis and even death. Due to its increasing incidence, oral surgeons will inevitably be faced with the management of these patients. To limit the risk of crises, our goal is to share recommendations for the management of sickle cell patients in oral surgery. The vaso-occlusive crises (VOC), heart attacks and chronic anemia endured by these patients cause chronic lesions in various organs. Complications include retinal disease, avascular necrosis, priapism, neurological involvement (cerebrovascular accident), cardiomyopathy, lower limb ulceration, renal and hepatic dysfunction, and cardiopulmonary disease. These complications inevitably lead to an increase in mortality rate. Thorough knowledge of this pathology is essential for the management of these patients in oral surgery. Management strategies include prevention and diagnosis of oral lesions related to sickle cell disease and its treatment, as well as methods of preparation and execution of oral surgery procedures. We suggest guidelines for the management of these complications and implementation of preoperative, intraoperative and postoperative surgical protocols for both practitioners and patients.