Six indigenous medicinal plants species, Agapanthus inapertus, Cheilanthes hirta, Crassula capitella, Eriospermum flagelliforme, Euphorbia clavarioides and Pelargonium alchemilloides are used traditionally in South Africa to treat wounds without scientific evidence as wound healing agents. Consequently, this study sought to investigate the antioxidant and anti-inflammatory activities of these plants species as a first step towards their validation as wound healing agents. The 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), ferric reducing antioxidant power (FRAP), and β-carotene-linoleic acid model system (β-CLAMS) assays were used to test for antioxidant activity. The inhibition of the xanthine oxidase (XO), cyclooxygenase -2 (COX-2) and 15- lipoxygenase (15-LOX) as well as the extracts’ ability to preserve the cyclooxygenase-1 (COX-1) enzyme activity were used as anti-inflammatory models. Furthermore, the total phenolics, flavonoids and proanthocyanidins content were quantified using standard methods. Species, C. hirta displayed high flavonoid and proanthocyanidin content whilst C. capitella displayed high phenolic content, and good activity against the four used antioxidant models compared to standards, butylated hydroxytoluene and ascorbic acid. Majority of the extracts displayed significantly higher anti-xanthine oxidase activity, outperforming standard quercetin. The acetone extracts of A. inapertus (IC50 = 57.33 ± 0.30 µg/mL), E. flagelliforme (IC50 = 52.10 ± 0.98 µg/mL), P. alchemilloides (IC50 = 58.28 ± 0.94 µg/mL) and E. clavarioides water (IC50 = 50.53 ± 0.47 µg/mL) extract displayed moderate 15-LOX inhibition compared to standard, nordihydroguaiaretic acid (IC50 = 0.45 ± 0.01 µg/mL). The acetone extracts of C. capitella (IC50 = 3.16 ± 0.06 µg/mL), E. flagelliforme (IC50 = 1.13 ± 0.09 µg/mL), E. clavarioides (IC50 = 1.84 ± 0.18 µg/mL), P. alchemilloides (IC50 = 1.13 ± 0.14 µg/mL), and the E. clavarioides water extract (IC50 = 1.18 ± 0.11 µg/mL) displayed COX-2 inhibition comparable to that of standard, aspirin (IC50 = 1.11 ± 0.03 µg/mL). At some degree, all tested extracts preserved the activity of the COX-1 enzyme with the E. clavarioides acetone extract significantly preserving the activity of COX-1 (IC50 = 96.21 ± 0.18 µg/mL), compared to standard, aspirin (IC50 = 0.98 ± 0.06 µg/mL). The antioxidant and anti-inflammatory activities displayed by these medicinal plants support their application and beneficial effect in wounds healing and hold promising prospects as natural alternatives to the existing conventional treatments.