Portulacaria afra, is indigenous to South Africa and has been identified to have several medicinal properties according to traditional knowledge and few studies. The drive around this research is to evaluate the medicinal properties of the leaves, stems and for the first time the roots extracts of Portulacaria afra, using four solvents with different polarities. The aqueous (60°C), methanol, n-hexane and ethyl acetate whole plant extracts of P. afra were investigated for their phytochemical properties, antimicrobial and antioxidant activity. The phytochemical screening revealed that the methanolic and aqueous extracts of the leaves displayed high presence of secondary metabolites compared to n-hexane and ethyl acetate extracts. The methanolic leaves extracts showed strong presence of quinones, phenols, steroid and coumarins while the aqueous leaves extracts contained a moderate presence of saponins, terpenoids, quinones and coumarins. Ethyl acetate leaves extracts revealed a strong presence of tannins, moderate presence of phytosteroids and a low presence of volatile oil. Meanwhile, the leaves extracts with n-hexane showed a considerable amount of saponins with a moderate presence, and a low presence of tannins, volatile oils and terpenoids. The methanolic stems extracts displayed the most significant presence of secondary metabolites, showing a high presence of terpenoids, steroids, phenols and coumarins. The aqueous stems extracts showed a strong presence of glycosides with a moderate presence of saponins. However, ethyl acetate and n-hexane stems extracts displayed a few secondary metabolites with their concentration ranging from medium to low. The ethyl acetate roots extracts displayed a significant elevated amount of quinones with a strong presence. n-hexane roots extracts showed a moderate presence of volatile oil and a low presence of tannins and steroids. Methanolic roots extracts showed a moderate presence of coumarins and glycosides while aqueous roots extracts showed a low presence of glycosides. The overall highest total phenolics contents (TPCs) and total flavonoids contents (TFCs) in all the plant parts, were found to be in the methanol stems extracts and aqueous roots extracts respectively. Next to the methanol leaves and aqueous leaves extracts respectively. However, in the root’s extracts, the aqueous extracts showed the highest total phenolics content while the water extracts had the highest total flavonoids contents. The antimicrobial activities of P. afra whole plant extracts with the various four solvents were tested against three microorganisms Escherichia coli, Staphylococcus aureus and Streptomyces griseus using agar-well diffusion method. The Antimicrobial activity of the n-hexane extracts of the leaves, stems and roots of P. afra presented a wide range of inhibition against all the test microorganisms, ethyl acetate leaves extract showed a considerable effect against Staphylococcus aureus while the methanolic extracts were not active. Aqueous roots extracts demonstrated a strong antimicrobial activity against Staphylococcus aureus while the other extracts were not active. The zones of inhibition ranged from 13 to 24 mm for the plant extracts. The antioxidant activity potential of the aqueous, methanol, n-hexane and ethyl acetate extracts of P. afra leaves, stems and roots extracts were observed through a 2, 2 diphenylpicryhydrazyl (DPPH) free radical assay, hydrogen peroxide scavenging (H₂O₂) and metal chelating activity assay. Ethyl acetate roots extracts exhibited the strongest hydrogen peroxide scavenging activity compared to the other extracts. Meanwhile, aqueous stems extracts showed the highest antioxidant activity against DPPH radical. Aqueous and n-hexane roots extracts displayed the strongest metal chelating ability. These findings reveal the efficacy of the use of several solvents with different polarities for effective and more accurate extraction of various compounds and indicate that the antimicrobial and antioxidant activity of P. afra parts are dependent on the solvent extracts.