| Summary: | Skin diseases are a worldwide issue, accounting for approximately 34% of all occupational illnesses. The aim of this study was to investigate medicinal plants used to treat wounds and skin diseases in the eastern Free State Province of South Africa. An ethnobotanical survey was conducted to gather information from traditional healers on plants they use to treat human ailments. Plants were collected and then investigated for antimicrobial, antioxidant and anti-inflammatory properties using standard assays. <i>Cotyledon orbiculata</i>, <i>Dioscorea sylvatica</i>, and <i>Lycopodium clavatum</i> had the highest frequency of citation (RFC) values among the 22 plants reported. Saponins, flavonoids, terpenoids, alkaloids, anthraquinones, and tannins were found in the phytochemical examination. <i>L. clavatum</i> had the greatest activity against <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> at 0.39 mg/mL and 0.098 mg/mL, respectively. <i>C. orbiculata</i> and <i>D. sylvatica</i> extracts showed significant antifungal activity between 0.39 and 1.56 mg/mL. Antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radicals was found in all extracts. The extracts had significant anti-inflammatory action against the 5-lipoxygenase enzyme, with IC<sub>50</sub> values ranging from 0.02 to 0.49 g/mL. The usage of <i>C. orbiculata</i>, <i>D. sylvatica</i>, and <i>L. clavatum</i> in the treatment of skin problems in the Eastern Free State of South Africa was verified in this research.
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