Methamphetamine (METH) is a potent and highly addictive psychostimulant and one of the most widely used illicit drugs, the abuse of which has become a severe public health problem worldwide. A growing amount of evidence has indicated potential connections between gut microbiota and mental disorders induced by METH and associations with neural and metabolic pathways. The present study aimed to explore the relationship be-tween fecal microbial alterations and neuropsychiatric diseases in METH addictions. Thus, mental disorders and gut microbial alterations were analyzed by self-rating depression (SDS) and anxiety (SAS) scales and 16 S rRNA gene sequencing, respectively. Our results showed that increased SDS and SAS indices and decreased alpha di-versity indicated more serious mental disorders and lower bacterial diversity in METH users than in the age-matched healthy control group. The gut microbial composition in female METH users was also significantly altered, with reductions in hydrogen-producing bacteria, including Bacteroides and Roseburia. Molecular hydrogen (H2) is spontaneously produced by intestinal bacteria in the process of anaerobic metabolism, which is the main pathway for H2 production in vivo. Numerous studies have shown that hydrogen intervention can significantly improve neuropsychiatric diseases, including Alzheimer's disease and Parkinson's disease. Our results showed that hydrogen intervention, including drinking and inhaling, significantly alleviated mental disorders induced by METH abuse, and the inhalation of hydrogen also altered gut microbiota profiles in the METH abusers. These results suggest that hydrogen intervention has potential therapeutic applicability in the treatment of mental disorders in METH abusers.