Cissus rotundifolia (Forssk.) Vahl. (Vitaceae) is a wild plant that is commonly used by communities from rural areas as a food and medicine. There are limited studies on the phytochemical composition and the impact of soil quality on the elemental distribution in this plant. In this study, we report a phytochemical analysis to identify the phytocompounds responsible for the reported biological activities of C. rotundifolia. We also examined the impact of soil quality on elemental uptake by the edible parts of C. rotundifolia collected from eight geographical locations in KwaZulu-Natal (South Africa) to assess the nutritional benefits and potential heavy metal toxicities. Three secondary metabolites (stigmasterol, β-sitosterol, and pheophytin a) were isolated, and their structures were characterised by high-resolution mass spectrometry and nuclear magnetic resonance data. The plant was found to contribute adequately to the recommended dietary allowances for essential nutrients without exceeding tolerable upper intake limits and with low concentrations of toxic heavy metals. The average concentrations of microelements in the edible parts were found to be in decreasing order of Fe>Mn>Se>Zn>Cu>Cr>Ni>Co. The bioaccumulation factors indicate that the plant controls the uptake of metals from the soil and would make a good indicator and biological monitor for cadmium toxicity. However, a health risk assessment exposed carcinogenic risks on regular consumption of the plant obtained from sites close to pollution sources, such as roads and landfills. The findings from this study show the synergies when consuming medicinal plants and provide evidence for C. rotundifolia as a nutraceutical.