Objective To explore the Genome-wide DNA methylation in children and adolescents with bipolar depression and aggressive behavior. Methods A total of 45 pediatric bipolar disorder（ PBD） patients admitted to the Department of Clinical Psychology of People's Hospital of Xinjiang Uygur Autonomous Region from September 2019 to January 2021 were recruited， and divided into aggressive group（ n=16） and non-aggressive group（ n=29）. Five patients with PBD were enrolled from each group. Illumina Infinium HumanMethylation EPIC BeadChip 850K array， was applied to detect DNA methylation status in peripheral blood of these 10 patients. Differential methylation loci were filtrated according to the Diffscore and methylation differences（ Delta-beta score）， together with Genome Studio software. The Database for Annotation， Visualization and Integrated Discovery（ DAVID） online database was used to analyze the functional enrichment of methylated genes. Two genes were verified by pyrosequencing in peripheral blood of the aggressive group and the non-aggressive group. Results There were differences in 172 hypermethylated loci， including 87 hypermethylated genes， between the samples of the attack group and the non-attack group. There were 148 different hypomethylated loci， including 74 hypomethylated genes. Differential methylation sites exist on each chromosome and are mainly distributed in other regions of 5'-Cytosine-phosphoric-guanine-3（' CpG） island. The peak value of methylation β in the aggressive group was about 0.63. The peak values of methylation β in non-aggressive group were about 0.40 and 0.85. Gene Ontology analysis results showed that differential methylated genes were involved in biological functions such as axonal orientation. In pathway analysis， it was involved in mucin-type O-glycan biosynthesis pathway. In pyrosequencing verification， the methylation rates of dihydropyrimidinase like 2（ DPYSL2） gene in the two groups were（ 27.438±17.874）% and（ 27.345±18.832）%， respectively. There wass no statistical significance between the two groups（ P=0.987）. The methylation rates of ABI family member 3 binding protein（ ABI3BP） gene in the two groups were（ 84.188±25.761）% and （78.586±23.567）%， respectively. There is no statistical significance between the two groups（ P=0.113）. Conclusions There were differences in methylation loci and genes between the aggressive group and the non-aggressive group， which provided a basis for identifying the causes of aggressive behavior in children and adolescents with bipolar depression.