<p>Cd is a ubiquitous and toxic heavy metal, characterized by environmental persistence and bioaccumulation, which presents high risks to agricultural production and human health. In this review, natural countermeasures against Cd toxicity are systematically categorized into inorganic substances, active natural products, and microorganisms. We discuss these compounds as protectants and the shared and distinct mechanisms by which they reduce metal toxicity, including competitive uptake, chelation, antioxidant enhancement, and gene regulation. A comprehensive review of studies published in recent years highlights the great influence on protective efficacy by compound-specific mechanisms, including the role of essential metals in competitive uptake and induction of particular antioxidant pathways through phyto-chemical exposure. Despite this, major knowledge gaps are still left to be filled, especially concerning the combined impact of treatments and their performances under field conditions or long-term sustainability. The aim of the present study is to explain the mechanisms for their protective effects, and these results offer an overview to contribute to developing environmentally friendly methods for Cd phytoremediation. This literature review comprehensively summarizes the up-to-date comprehension of natural protection against Cd, and will provide an insight for the subsequent investigations on the practical applications in agriculture, environmental treatment, and public health to ensure food system safety and land reduction of pollutants from the contaminated environment.</p>