In the era of sustainable development, the current focus is on the development of the new tools to control the pest infestation on different crops with the help of plant secondary metabolites (PSM). The PSM, which are showing their effective role in the plant pest protection, are terpenoids, alkaloids, phenolics, and glycoalkaloids. These compounds exhibit their insecticidal activity with their different mode of action. Among the biotic stresses, herbivore attack is one of the major one that leads to the damage of the tissue which activates the defense signaling inside the plant. The plant contains the primary metabolite that is responsible for the growth and development of the plant, and the secondary metabolite works as a defense against herbivory. In this chapter, we have discussed about the secondary metabolites as a defense compound, its classification, distribution, and their mode of action. The generalized mode of action as well as the specified mode of action of PSM has been covered. PSM generally inhibit the cholinesterase enzyme activity and block the membrane channels which lead to the neurotoxic effect inside the insect, and it becomes fatal for the insect survival. In some cases, there is the formation of the reactive oxygen species which leads to the insect death via membrane disruption. PSM also cause the hormonal imbalance; affect permeability of the cell membrane, disruption of cell membrane, and antibiosis effect; inhibit neuronal signal transduction; inhibit the growth and development; and many others. Plant secondary metabolites’ lethal effect also depends upon the dose. The high target specificity, mechanism of action, and unique structural property against the specific insect may lead to the success in development of the eco-friendly pesticides.