Rotenoids and neonicotinoids are two major classes of insecticides that differ significantly in their origin, mode of action, and toxicity, reflecting their distinct chemical nature and interactions with insect physiology. Rotenoids are naturally occurring compounds derived primarily from the roots of plants belonging to the *Derris*, *Lonchocarpus*, and *Tephrosia* genera. These compounds, including rotenone, are extracted and used as botanical insecticides, often classified as botanical rotenoids. In contrast, neonicotinoids are synthetic compounds developed through chemical synthesis to mimic certain natural alkaloids, such as nicotine, found in tobacco plants. Neonicotinoids, including imidacloprid, thiamethoxam, and acetamiprid, represent a modern class of systemic insecticides widely used in agriculture due to their high efficacy and selectivity. The mode of action of rotenoids is primarily through the inhibition of mitochondrial electron transport. Rotenone specifically targets complex I (NADH:ubiquinone oxidoreductase) in the mitochondrial