Ten South African Commiphora (Burseraceae) species were investigated to validate their use in traditional healing rites. The leaf and stem extracts of each species were analysed for the anti-oxidant (ABTS and DPPH assays), antimicrobial (MIC and death kinetic assays), anti-inflammatory (5-LOX assay), anticancer (SRB assay) properties, as well as the cytotoxic effects (tetrazolium-based assay). The best anti-oxidant activity (ABTS assay) was observed for the stem extracts of Commiphora tenuipetiolata IC50 = 5.10 μg/ml), Commiphora neglecta (IC50 = 7.28 μg/ml) and Commiphora mollis (IC50 = 8.82 μg/ml). Extracts generally exhibited poor anti-oxidant activity in the DPPH assay, with the exception of Commiphora schimperi (stem), Commiphora neglecta (stem), Commiphora tenuipetiolata (stem and leaf), and Commiphora edulis (stem), with IC50 values ranging between 7.31 and 10.81 μg/ml. The stem extracts exhibited moderate to good 5-LOX inhibitory activity with Commiphora pyracanthoides (stem) displaying the greatest inhibitory effect (IC50 = 27.86 ± 4.45 μg/ml). For the antimicrobial (MIC) assay, a greater selectivity was exhibited by the extracts against the Gram-positive bacteria (0.01-8.00 mg/ml) and the yeasts (0.25-8.00 mg/ml) than against the Gram-negative bacteria (1.00-8.00 mg/ml). Using death kinetic studies (time-kill studies), the rate at which Commiphora marlothii (stem) kills Staphylococcus aureus over a 24 h period was determined. Mostly, a concentration-dependent antibacterial activity was observed beginning after ca. 30 min. All concentrations exhibited antibacterial activity, with complete bactericidal effect achieved by the 24th hour. The most active Commiphora species against the HT-29 cells (SRB anticancer assay) were Commiphora glandulosa (leaf and stem) and Commiphora marlothii (leaf). The MCF-7 cells (SRB anticancer assay) exhibited the highest sensitivity to indigenous Commiphora species, with Commiphora edulis (leaf and stem), Commiphora glandulosa (leaf and stem), Commiphora marlothii (leaf), Commiphora pyracanthoides (leaf and stem), Commiphora schimperi (stem), and Commiphora viminea (stem) all possessing a percentage inhibition greater than 80% at 100 μg/ml. Commiphora glandulosa (leaf and stem) and Commiphora pyracanthoides (leaf and stem) were the two most active species against the SF-268 cells (SRB anticancer assay), with IC50 values ranging between 68.55 ± 2.01 and 71.45 ± 1.24 μg/ml. The majority of the Commiphora extracts were largely non-cytotoxic against Graham human kidney epithelial cells when investigated in the MTT assay.