The investigation of Tylosema esculentum (Morama) husks, cotyledons, and tuber yielded griffonilide 2, compound 1, griffonin 3, gallic acid 4, protocatechuic acid 5, β-sitosterol 6, behenic acid 7, oleic acid 8, sucrose 9, 2-O-ethyl-α-d-glucopyranoside 10, kaempferol 11 and kaempferol-3-O-β-d-glucopyranoside 12. The structures of the isolates were determined by NMR, HR-TOF EIMS, IR and UV–vis spectroscopy, and by comparison with literature data. The husk EtOAc and n-butanol extracts demonstrated >90% DPPH radical scavenging activity at concentrations of 25, 50 and 250μg/mL. Furthermore the husk extracts showed higher total phenolic content (233mg GAE/g). The extractives exhibited minimum inhibitory quantities of 50–100μg or no activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans. The tuber extracts were inactive against Caco-2 and Hela cell lines, while the husk extracts showed low activity against Caco-2 and Vero cell line with IC50 values >400μg/mL. The GC–MS analysis showed the beans and tuber non-polar (n-hexane) extracts major constituents as fatty acids.