<p>Cadmium (Cd) contamination in agricultural ecosystems represents a persistent One Health challenge, threatening livestock productivity, food safety, and human health. Once ingested, Cd bypasses efficient excretion, accumulates in the liver, kidney, bone, and reproductive tissues, and provokes oxidative stress, inflammation, and metabolic dysfunction. This review presents a critical examination of experimental evidence on nature-derived mitigation strategies-including phytochemicals, essential trace minerals, vitamins, and probiotics-with emphasis on their molecular, genetic, and metabolomic mechanisms of action. Phytochemicals such as polyphenols and terpenoids modulate oxidative and inflammatory signaling, minerals such as Zinc (Zn) and Selenium (Se) induce metallothionein (MT) expression and antagonize Cd absorption, vitamins enhance redox homeostasis, and probiotics bind Cd in the gut and restore microbial and immune balance. Most of the evidences suggest the role of Zn, Se, and selected probiotic strains in reducing tissue Cd burden, while phytochemicals show mechanistic promise but limited bioavailability in ruminants. To address these gaps, three integrative frameworks-Triple-T (Targeting, Timing, Tuning), Gastrointestinal Fate Determinism (GFD), and a Mitigation Potential (MP)- that prioritize interventions by biological efficacy, delivery feasibility, and translational potential in being proposed. Although nature-derived strategies present a sustainable avenue for combating Cd toxicity, their successful integration into livestock production systems necessitates interdisciplinary efforts. Overcoming translational barriers through advanced delivery systems, species-specific dosing, and cost-effective formulations is imperative to safeguard animal health, ensure productivity, and uphold One Health principles.</p>