The emergence of the core traits in autism spectrum disorder (ASD), which includes altered social interactions, communication, and repetitive movements, stems from impaired excitation-inhibition (E/I) balance of key brain structures (i.e. the prefrontal cortex, hippocampus, and striatum). Whilst interneuron hypofunction has been attributed to ASD presentation, no research has attempted to restore their activity from early stages of brain development to alleviate core traits. Here, searching for molecular regulators of interneuron function, we examined the involvement of the Neurokinin 3 receptor (NK3R) in the pathophysiology of ASD in mice. We found that NK3R expression was disrupted and was correlated with functional deficits in interneurons in mouse models of ASD. We assessed whether manipulating developmental NK3R function could tune interneuron activity and enable appropriate circuit maturation in ASD. Using systemic treatment with specific NK3R agonists in pups, we restored interneuron morpho-functional properties and normalized the developmental trajectory of the cortico-hippocampo-striatal ensembles that underpin the ASD traits. We also discovered that the NK3R-dependent modulation of the early postnatal interneuron activity prevented the behavioral manifestations of ASD in the adult, in three mouse models. Overall, this study reveals that normalizing NK3R function during the first postnatal weeks is sufficient to restore normal interneuron activity, the establishment of functional brain circuits and is efficient in preventing the core symptoms of ASD in mice. This work therefore opens the path to novel therapeutic strategies and translational applications in ASD and other neurodevelopmental disorders involving interneuron dysfunction.