Molecular docking study to evaluate ligand interaction using in silico molecular docking with validated trypanosome brucei protein target that is available from Protein Data Bank (PDB code – 13PK) and assessment of the ‘drug-like’ using a set of calculated molecular descriptors, of the collection of 105 natural products from Africa exhibiting in vitro or in vivo activities against trypanosome brucei. Inhibition constant and free energy of binding were used to assess ligand interaction and Lipinski’s ‘Rule of Five’ was used to evaluate oral availability by making use of popular parameters like Molecular Weigth (MW), predicted lipophilicity (log P), number of Hydrogen Bond Donors/Acceptors and Number of Rotatable Bonds (NRB). The drug-like properties of the studied compounds were compared to that of the Dictionary of Natural Products. Our results revealed that 76.19 % and 66.67 % of the studied compounds have binding energy (-8.32 to -1.84 Kcal/mol) inhibition constant (Ki) (802 nM to 9.09 µM) which are comparable to the native ligand. Also, 99, 66 and 23 of our dataset fall within the recommended range for ‘drug-like’, ‘lead-like’ and ‘fragment-like’ respectively. This study aims at attracting the interest of medicinal and pharmaceutical researchers to natural sources (particularly Africa natural products) in search for anti-trypanosomal lead compounds.