The developing brain establishes mature neural circuits through processes such as neuronal differentiation and synapse formation. However, these processes are susceptible to disruption by external factors, including exposure to environmental chemicals. These disruptions have been associated with neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This underscores the increasing significance of developmental neurotoxicity (DNT) assessment. However, conventional DNT testing methods are extremely costly and time-consuming, making broad in vivo coverage of the large number of chemicals in use impractical. Therefore, there is an increasing international demand for more efficient, quantitative screening approaches. Bioluminescence imaging (BLI) using reporter transgenic (Tg) mice enables the noninvasive visualization of gene expression and signal transduction in living animals and has been widely applied in fields such as oncology and regenerative medicine. This review highlights recent advances in the application of reporter Tg mice to assess DNT and explores their potential applications in DNT screening, chemical risk assessment, and future research on developmental neurotoxicity.