This study aimed to investigate the effects of swertiamarin (STM) on the gut microbiota–short-chain fatty acids (SCFAs) metabolic axis in mice with ulcerative colitis (UC) and elucidate the underlying mechanisms by which STM alleviates UC. Thirty C57BL/6J mice were randomly divided into three groups: control group, model group, and STM group (100 mg/kg). A 2.5% dextran sulfate sodium (DSS) solution was used to induce the ulcerative colitis mouse model. The STM group received STM solution via oral gavage for ten days. Daily changes in body weight were recorded. Pathological and functional alterations in the colon were observed using hematoxylin and eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining. Serum inflammatory cytokines were measured, gut microbiota was analyzed via 16S rRNA sequencing, and SCFAs content in intestinal contents was quantified using GC-MS. Compared with the model group, STM treatment significantly attenuated body weight loss (P < 0.05), colon length shortening (P < 0.05), and intestinal epithelial damage in mice, while promoting significant increases in goblet cell numbers and mucus secretion (P < 0.01). Additionally, STM treatment reduced serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in UC mice (P < 0.05). STM did not alter the richness or diversity of gut microbiota across experimental groups; however, it significantly restructured the microbial community composition in UC mice. At the phylum level, STM decreased the relative abundances of Firmicutes, Epsilonbacteraeota, and Deferribacteres while increasing Proteobacteria and Verrucomicrobia. At the genus level, STM reduced the relative abundances of Streptococcus, Bacteroides and Helicobacter but increased Akkermansia. GC-MS results showed that STM significantly elevated acetic acid (P < 0.05) and butyric acid (P < 0.01) levels compared to the model group. In summary, STM may alleviate DSS-induced ulcerative colitis by inhibiting the secretion of pro-inflammatory factors, modulating the gut microbiota structure, and promoting the production of SCFAs.