Although thousands of people worldwide suffer from sickle cell disease, the most common form of an inherited blood disorder, there are only a handful of available treatments available to combat the significant morbidities, lifelong challenges, reduced quality of life, and early mortality rates in patients. The resources available are also inaccessible to many either due to price or the possibility of adverse effects such as myelosuppression. Thus, to discover more effective and affordable treatments for patients with sickle cell disease, we investigated the anti- sickling effect of SCD-101, a botanical extract often utilized for medicinal purposes in Nigeria and other West African countries. After conducting multiple in-vitro sickling assays, we discovered that there are one or more small molecules located in fractions of SCD-101 that confer the indigenous plant with anti-sickling activity. In view of the outcome of this study, SCD-101 may be a promising option for the treatment of patients with sickle cell disease.