Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by difficulties in communication, social interaction, and repetitive behaviors. Considering its multifactorial origin and multisystem involvement, this single-case report applies a complex naturopathic intervention—the Katia Dolle Method® (KDM)—integrating immunonutrition, targeted supplementation, parental coaching, structured neurostimulation, and periodic biological monitoring over 21 months. A 4-year-old girl diagnosed with moderate–severe ASD (baseline ATEC = 112) underwent the KDM program (March 2023–November 2024). Outcomes were tracked with ATEC, DP-3, and SENA, alongside blood/urine/stool biomarkers. Results show a reduction of ASD severity from severe to mild (ATEC = 16, −85.7%) in 21 months, and a DP-3 General Development Index increase from 62 to 91 (≈ +29 points, ~2.4 SD) in the last 12 months, exceeding maturational expectations (“catch-up” effect). SENA indices improved consistently (problem indices decreased, personal resources increased). No regressions or adverse effects were observed. This case illustrates the clinical applicability of a complex, multimodal naturopathic approach for ASD within a PNIE framework and supports the need for prospective controlled studies. Figures and underlying data are provided as supplementary materials.