Despite commercial interest and ethnobotanical data, the pharmacological activities of a number of indigenous Pelargonium species hitherto remain poorly explored. The acetone extracts of twenty-one Pelargonium species (section Pelargonium) were included in this study. Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, potent anti-oxidant activity was observed for the crude extracts of P. betulinum and P. crispum (IC50 values of 4.13 ± 0.14 μg/ml and 4.49 ± 0.18 μg/ml, respectively compared to ascorbic acid, IC50 = 4.72 ± 0.14 μg/ml). The antimicrobial (both bacterial and fungal) potential of the extracts was evaluated by using the minimum inhibitory assay. The crude extracts of P. glutinosum (SBG), P. pseudoglutinosum, P. scabrum and P. sublignosum exhibited considerable antimicrobial activity against the Gram-positive test bacteria, with P. pseudoglutinosum demonstrating the highest inhibitory activity (MIC = 39 μg/ml); however the aforementioned species were also relatively cytotoxic. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) cellular viability assay was used to determine the toxicity of the acetone extracts against transformed human kidney epithelial (Graham) cells. The acetone extracts of P. sublignosum and P. citronellum (NBG) displayed the highest toxicities (IC50 = 11.89 ± 1.54 μg/ml and 19.14 ± 0.98 μg/ml, respectively). The results from the toxicity assay suggested that the antimicrobial activity of the extracts may be ascribed to general cytotoxic effects. Considering all the results collectively, Pelargonium cordifolium appears to be the most promising species requiring further investigation.