Penthorum chinense Pursh (P. chinense) has been traditionally used as hepatoprotective food and medicine for hundreds of years due to its significant antioxidant and anti-inflammatory activities. However, the efficacy and mechanisms of action of P. chinense in type 2 diabetes mellitus were not fully understood. In this study, we found that P. chinense extract (PCP) supplementation resulted in reduced body weight and hyperglycemia, improved islet β-cell mitochondrial swelling and insulin sensitivity, and decreased inflammatory cytokines expression in spontaneously diabetic db/db mice. 16S rRNA gene sequencing of fecal samples showed that PCP administration decreased the abundance of Firmicutes and increased the proportion of Bacteroidetes at the phylum level. Moreover, Muribaculum, Barnesiella, Prevotella, and Mucinivorans were enriched, with Desulfovibrio and Lactobacillus lowered at the genus level in db/db mice with PCP supplementation. These results suggested that PCP may ameliorate hyperglycemia, insulin resistance, and inflammation by remodeling the gut microbiota in db/db mice.