Background <p>Lipid metabolism and its regulatory molecules, especially adipokines, have gained significant attention in recent pathogenesis research of autism spectrum disorder (ASD).</p> Aims <p>To evaluate serum fatty acid-binding protein 4 (FABP4) levels as a potential biomarker for autism spectrum disorder (ASD), comparing them to levels in children with intellectual disabilities and typically developing peers, and to determine whether variations in FABP4 can effectively differentiate children with ASD from those with intellectual disabilities.</p> Methods <p>A comparative cross-sectional study was conducted with 90 children aged 3 to 12 years, divided into three groups: 30 children with autism spectrum disorder (ASD), 30 with Intellectual Disability (ID), and 30 healthy controls. Serum samples were collected and analyzed for FABP4 levels. Demographic characteristics, cognitive function and severity of ASD disease were collected and analyzed in relation to the FABP4 level.</p> Results <p>Mean serum FABP4 levels were significantly lower in both ASD and ID groups compared with controls (<i>p</i> &lt; 0.001). FABP4 demonstrated excellent diagnostic performance for differentiating ASD from controls (AUC = 1.00, cut-off &lt; 3.99 ng/mL, 100% sensitivity and specificity) and ID from controls (AUC = 0.989, cut-off &lt; 3.77 ng/mL, 96.7% sensitivity and 100% specificity). However, FABP4 showed limited ability to distinguish ASD from ID (AUC = 0.63, <i>p</i> = 0.090). No significant correlation was found between FABP4 levels and age, BMI, and ASD severity (<i>p</i> &gt; 0.05).</p> Conclusion <p>The data suggest that FABP4 may serve as a marker of neurodevelopmental dysfunction, rather than functioning as a specific biomarker for diagnosing autism.</p> Clinical trial number <p>Not applicable.</p>