Sickle cell disease (SCD) is a genetic disease characterized by red blood cells that assume an abnormal, rigid sickle shape in hypoxic conditions. Recent reports revealed also that SCD patients are sensitive to bacterial infections. Among microbial agents, Staphylococcus aureus is the bacteria most implicated in septicemia and osteomyelitis in SCD patients. The aim of the present study was to extract and evaluate the bioactivity of anthocyanins and organic acids from Gnetum africanum and Grewia coriacea against SCD and associated bacteria. The antisickling bioassay and antibacterial activity were carried out using Emmel and microdilution methods respectively. The results revealed that anthocyanins and organic acids extracts of these plants possess antisickling and antibacterial activities. The calculated values of sickle erythrocytes normalization rates were 78% and 82% respectively for anthocyanins and organic acids extracts of Grewia coriacea, and 88% for organic acids extract of Gnetum africanum. The MIC values of plant extracts against all tested bacteria were < 1000 µg/ml. MRSA ATCC 1625 and MSSA ATCC 5668 were sensitive to organic acids extract of G. coriacea (MIC = 7.813 µg/ml) while Escherichia coli ATCC 25922 was sensitive to anthocyanins extract of G. coriacea (MIC = 62.5 µg/ml). On the other hand, Staphylococcus aureus ATCC 25923 strains were sensitive to organic acids extract of G. africanum (MIC = 125 µg/ml). Staphylococcus aureus is the bacteria most implicated in septicemia and osteomyelitis in SCD patients. Medicinal plant extracts displaying at the same time antibacterial (against Staphylococcus aureus) and antisickling effects could be useful in the management of Sickle cell disease. This study provides for the first time a scientific basis for the antibacterial and antisickling activities of anthocyanins and organic acids extracts from Grewia coriacea and organic extracts of Gnetum africanum justifying thus their use in African traditional medicine.