The transformation of trace metals (TMs) in natural environmental systems has created significant concerns in recent decades. Ultramafic environments lead to potential risks to the agricultural products and, subsequently, to human health. This unique review presents geochemistry of ultramafic soils, TM fractionation (i.e. sequential and single extraction techniques), TM uptake and accumulation mechanisms of ultramafic flora, and ultramafic-associated health risks to human and agricultural crops. Ultramafic soils contain high levels of TMs (i.e. Cr, Ni, Mn, and Co) and have a low Ca:Mg ratio together with deficiencies in essential macronutrients required for the growth of crops. Even though a higher portion of TMs bind with the residual fraction of ultramafic soils, environmental changes (i.e. natural or anthropogenic) may increase the levels of TMs in the bioavailable or extractable fractions of ultramafic soils. Extremophile plants that have evolved to thrive in ultramafic soils present clear examples of evolutionary adaptations to TM resistance. The release of TMs into water sources and accumulation in food crops in and around ultramafic localities increases health risks for humans. Therefore, more focused investigations need to be implemented to understand the mechanisms related to the mobility and bioavailability of TMs in different ultramafic environments. Research gaps and directions for future studies are also discussed in this review. Lastly, we consider the importance of characterizing terrestrial ultramafic soil and its effect on crop plants in the context of multi-decadal plans by NASA and other space agencies to establish human colonies on Mars.