Significant environmental risks are posed by heavy metal (HM) and metalloid contamination, which can harm plants by causing oxidative stress, nutritional imbalances, and disturbances in physiological and metabolic functions. The plants have developed a range of safety methods to fight various negative impacts, and secondary metabolites (SMs) are essential to lessen harmful effects and accumulation of HMs. The functions of important SMs, such as flavonoids, phenolics, alkaloids, terpenoids, carotenoids, and sulfur-containing compounds, in boosting plant resistance to stress caused by metals are examined in this chapter. Through metal chelation, sequestration, antioxidant defense, and structural component reinforcement, these metabolites aid in detoxification. Furthermore, their biosynthesis under metal stress is influenced by regulatory processes like transcription factors, hormone signaling, and epigenetic alterations. These metabolites’ potential uses in crop development and phytoremediation techniques are also covered, underscoring their importance in environmentally friendly farming practices and sustainable agriculture. The chapter concludes with future perspectives on integrating SM-based strategies to develop metal-tolerant and climate-resilient crops.