Proliferation of acute inflammation under pathological conditions makes targeting the pro-inflammatory enzymes a therapeutic intervention. The inflammation process contributes significantly to the appearance of the skin as a result of scarring and dark spots that develop. Inflammation is a normal physiological process employed to remove tissue damage due to the barrier breach of the skin. This study aimed to evaluate the inhibition and induction of enzymes associated with skin inflammation by 10 medicinal plants used traditionally for skincare and beauty in South Africa. Plants were initially examined for their total phenolic and flavonoid contents. Acetone and water extracts of the selected plants were assayed for their inhibitory activities of secretory phospholipase A2 (sPLA2), lipoxygenase (15-LOX) and cyclooxygenase (COX) enzymes using an inhibitor screening assay kit (Cayman Chemical, Ann Arbor, MI). The total phenolic content and flavonoid content were significantly high for Cassipourea flanaganii (Schinz) Alston. Extracts of Aloe ferox Mill and Plantago lanceolata L yielded a high content of total phenols and flavonoids, respectively. Water and acetone extracts of C. flanaganii and Chenopodium album L exhibited notable inhibitory activity against sPLA2 with IC50 values of 12.34 and 10.75 μg/mL, respectively. Water and acetone extracts of C. flanaganii exhibited moderate inhibitory activity of 15-LOX enzyme with IC50 values of 16.72 and 21.59 μg/mL, respectively. Water extracts of C. album also inhibited the activity of 15-LOX enzyme with an IC50 value of 18.99 μg/mL. Water extracts of Haemanthus albiflos Jacq, Ruta graveolens L, A. ferox, C. flanaganii and Clausena anisata (Willd.) Hook.f. ex Benth had a significantly high inhibitory activity against COX-2 enzyme with IC50 values ranging from 4.23 to 6.89 μg/mL. Furthermore, acetone extracts of Rorippa nasturtium-aquaticum (L.) Hayek, P. lanceolata and A. ferox significantly inhibited the activity of COX-2 with IC50 values ranging from 2.69 to 4.36 μg/mL. The observed selective inhibition of COX-2 enzyme by extracts of C. flanaganii, P. lanceolata and R. nasturtium-aquaticum is significant when screening for natural inhibitors with less risk of gastro-intestinal health effects. The selective inhibition of COX-2 enzyme is beneficial in modulation of skin inflammation during pathological conditions. Therefore, extracts from these plants can be incorporated in beauty formulations intended for treatment of chronic inflammation of the skin.