A comprehensive search of PubMed, Embase, and Cochrane databases identified randomized clinical trials evaluating non-drug interventions — defined as therapies not involving prescription psychotropic medications — including behavioral, digital, and nutritional approaches aimed at improving Social Responsiveness Scale (SRS) scores. Studies not meeting these criteria were excluded. Data were extracted, and analyses were performed using R Studio 4.3.1. Appropriate models accounted for heterogeneity, and pooled estimates were generated. Results were interpreted considering potential biases and limitations using the Risk of Bias 2 (RoB2) tool.

Fifty-six studies, comprising 117 treatment arms and 3,261 participants, were included. The network meta-analysis showed that, compared with placebo, the most effective interventions for reducing SRS scores were metaverse-based skills training (MD: –21.74; 95% CrI [–37.46, –6.28]), vitamin B12 supplementation (MD: –8.97; 95% CrI [–21.01, 3.04]), and high-dose vitamin A (MD: –4.13; 95% CrI [–17.00, 9.35]). Only metaverse-based skills training demonstrated a statistically significant improvement over placebo.

Metaverse-based skills training was the only non-drug therapy to significantly improve SRS scores compared to placebo, highlighting its potential as a promising intervention for ASD. However, current evidence on efficacy and safety is preliminary; thus, routine use of these approaches, including nutritional supplementation, cannot yet be recommended.