Xenobiotics could be defined as any foreign substances that neither provide any nutritional benefit to the organism nor could be metabolized in order to release energy. With the progression of modernization, humans, animals, and plants are continually subjected to numerous chemical substances that produce toxicity. The xenobiotics lead to the production of reactive oxygen species, which cause oxidative stress, leading to damage in cellular components. Unlike animals, plants do not have an elaborate excretory system. However, they can detoxify the xenobiotics by generating enzymatic and non-enzymatic antioxidant defense mechanisms. Secondary metabolites play a vital role in detoxification and the defense against oxidative stress. Therefore, plants act as an imperative sink for chemicals that are harmful to the environment as well as to living beings. In plants, xenobiotic metabolism occurs in three stages. First is modification, which involves the conversion of toxic xenobiotics into less toxic ones by chemical methods. Second is conjugation: combining xenobiotics with other substances to increase their solubility, facilitating their elimination from the plant. Third, compartmentalization involves storage or isolation of conjugated xenobiotics in specific parts of the plant, preventing damage to cellular functions. This chapter provides detailed insights into the processes involved in the detoxification of xenobiotics by plants.