α-Synuclein (α-syn) and tau proteins are thought to be related with the synaptic loss and cell death underlying several important neurodegenerative diseases. The aim of our study was to investigate serum α-syn and tau levels in autism. Serum levels of α-syn and tau were measured, and autism spectrum disorder (ASD) severity was assessed at admission using the Childhood Autism Rating Scale (CARS) total score. The mean CARS score of the autism group on admission was 47.91 points (SD: 5.97). The results indicated that the mean serum α-syn and serum tau levels were significantly (p < 0.001) lower in children with ASD as compared with normal cases (33.01 ± 20.78 and 55.19 ± 15.34 ng/mL and 241.23 ± 290.5 and 509.78 ± 269.25 ng/mL, respectively). There was a significant positive correlation between serum α-syn levels and serum levels of tau identified by Pearson correlation analysis (r = 0.922, n = 28, p < 0.001). Synaptic abnormality in autism may result from microglial activity. Furthermore, α-syn and tau aggregation may lead to synaptic dysfunction, and this may contribute to either neuronal or synaptic dysfunction or neurodegeneration. Our preliminary study suggests that low levels of serum α-syn and tau may be implicated in the relationship between synaptic activity and autism.