<p>Autism Spectrum Disorder (ASD), a group of highly heterogeneous and multifactorial neurodevelopmental disorders, is characterized by core clinical manifestations, including social deficits and repetitive stereotyped behaviors. Although its etiology involves both genetic and environmental factors, the exact pathogenesis remains elusive. Recent biological studies have untangled a pathological framework related to the “immune-neurodevelopmental axis”, which has emerged as a potential paradigm for deciphering the complex mechanisms underlying ASD. In this framework, adaptive and innate immunity dysfunctions are thought to potentially contribute to disease progression. This review integrates evidence from clinical cohort studies and animal models to elucidate the functional phenotypic alterations of the three major peripheral immune cell subsets in ASD. Furthermore, it explores the multidimensional cascade of pathogenic mechanisms in which peripheral lymphocyte phenotypes may be involved, thereby providing collective evidence to support the future development of immune-modulatory therapeutic strategies for ASD.</p>