Metabolic signals play an important function in regulating biological processes. Exposure to pollutants could induce certain transgenerational response of metabolic molecules, such as glucose and lipid. Additionally, transgenerational response of glucose, citric acid cycle (CAC), lipid, amino acid, and retinoic acid metabolism–related signals could be induced by pollutants. These metabolism-related signals participated in control of pollutant toxicity, suggesting the role of metabolism-related signals in modulating transgenerational pollutant toxicity. Toxicity of pollutants could be inhibited by treatment with some metabolic molecules, such as pyruvate, leucine, and retinoic acid, which further suggested the important function of metabolic molecules in regulating transgenerational pollutant toxicity.