Although orthodox medications are available for skin diseases, expensive dermatological services have necessitated the use of medicinal plants as a cheaper alternative. This study evaluated the pharmacological and phytochemical profiles of four medicinal plants (Drimia sanguinea, Elephantorrhiza elephantina, Helichrysum paronychioides, and Senecio longiflorus) used for treating skin diseases. Petroleum ether and 50% methanol extracts of the plants were screened for antimicrobial activity against six microbes: Bacillus cereus, Shigella flexneri, Candida glabrata, Candida krusei, Trichophyton rubrum and Trichophyton tonsurans using the micro-dilution technique. Antioxidant activity was conducted using 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging and β-carotene linoleic acid models. Cytotoxicity was determined against African green monkey Vero kidney cells based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Spectrophotometric and Gas Chromatography-Mass Spectrometry (GC-MS) methods were used to evaluate the phytochemical constituents. All the extracts demonstrated varying degrees of antimicrobial potencies. Shigella flexneri, Candida glabrata, Trichophyton rubrum and Trichophyton tonsurans were most susceptible at 0.10 mg/mL. In the DPPH test, EC50 values ranged from approximately 6-93 µg/mL and 65%-85% antioxidant activity in the β-carotene linoleic acid antioxidant activity model. The phenolic and flavonoid contents ranged from 3.5-64 mg GAE/g and 1.25-28 mg CE/g DW, respectively. The LC50 values of the cytotoxicity assay ranged from 0.015-5622 µg/mL. GC-MS analysis revealed a rich pool (94-198) of bioactive compounds including dotriacontane, benzothiazole, heptacosane, bumetrizole, phthalic acid, stigmasterol, hexanoic acid and eicosanoic acid, which were common to the four plants. The current findings provide some degree of scientific evidence supporting the use of these four plants in folk medicine. However, the plants with high cytotoxicity need to be used with caution.