Background: Obesity is a common health problem among patients with schizophrenia, but the precise mechanisms are not fully understood. There has been much interest in the relationship between gut microbiome and development of obesity. Gender-dependent microbial alteration has been reported in previous studies. However, the gender factor in gut microbiome composition of schizophrenia patients has been less investigated. Our study aimed to identify differences in gut microbiota between schizophrenia patients with normal weight and central obesity and investigate the gender specific features. Method: Twenty participants (10 males, 10 females) with central obesity (CO) and 20 participants (10 males, 10 females) with normal weight (NW) were recruited from two rehabilitation wards in a psychiatric hospital in central Taiwan. Fecal samples from 40 participants were processed for microbiota analysis. The intestinal microbiota composition was analyzed using next-generation sequencing and QIIME software. Results: Significantly higher richness of gut microbiota at the class level (measured by the number of observed OTUs) was observed in female NW subjects than in female CO subjects (P = 0.033). Furthermore, female NW subjects showed higher alpha diversity at both phylum and class levels (measured by the Shannon, Simpson, and Inverse-Simpson indexes) compared with female CO subjects. Males showed no significant difference in alpha diversity between groups. Taxonomic analysis showed that female CO subjects had significantly lower abundance of Verrucomicrobia (P = 0.004) at the phylum level, reduced abundance of Akkermansia (P = 0.003) and elevated level of Prevotella (P = 0.038) and Roseburia (P = 0.005) at the genus level. Conclusions: The present results evidenced altered microbiome composition in schizophrenia patients with central obesity and further suggested the role of the gender factor in the process of gut dysbiosis.