Developmental and epileptic encephalopathy (DEE) is a genetic neurological disease affecting 0.27–0.54 per 1000 newborns, with a strong genetic association. Currently, the majority of known pathogenic genes in genetic DEE can be classified into six functional categories: ion channels, organelles and cell membranes, growth and development, synaptic function, neurotransmitters and receptors, DNA and RNA regulation, and signal transduction pathways. Emerging evidence suggests that inflammatory regulation may play a critical role in genetic DEE pathogenesis. Specifically, astrocyte and microglial activation contributes to neuroinflammation in genetic DEE, while pro-inflammatory cytokines disrupt neuron-glia interactions, exacerbating epileptic seizures and neuronal damage. Targeting the source mechanism of neuroinflammation in genetic DEE, such as the activation of astrocytes and microglia, and intervening from the source, is expected to be a new target for the treatment of genetic DEE.