Autism spectrum disorders (ASDs) are neurodevelopmental disorders, which consists of symptoms, such as, social dysfunctions, as well as, repetitive and restricted behaviors. Many animal model studies, which have mimicked genetic mutations in human patients, suggest that synaptic dysfunctions could be a potent underlying mechanism of ASDs. However, it is unknown whether early postnatal developmental processes are involved in later pathogenic changes in the brain. In this study, I show that early correction of a dysregulated synaptic function in young mice prevents manifestation of autistic-like phenotypes in adult mice. Shank2-/- mice, displaying autistic-like behaviors―social dysfunction, repetitive jumping and hyperactivity―and reduced NMDA receptor function at post-weaning stages after postnatal day 21 (>P21), showed earlier NMDA receptor hyperfunction at an pre-weaning age (~P14). Moreover, early suppression of NMDA receptor function (P7-21) by memantine prevented later NMDA receptor hypofunction, social-interaction deficits, and hyperactive locomotion at juvenile and adult stage. Interestingly, mRNA level of oxytocin after early memantine treatment was highly increased in Shank2-/- brain. Acute nasal administration of oxytocin rescued social dysfunction in Shank2-/- mice. These results suggest that specific time-window in which unique synaptic deficits are present and the intervention of NMDA receptor activity at that period could be a potent strategy to prevent autistic-like phenotypes in Shank2-/- mice.