Ulcerative colitis (UC), a chronic relapsing-remitting-inflammatory disorder affecting the colonic and rectal mucosa, poses significant challenges in the management of inflammatory bowel disease (IBD). This study investigated the therapeutic potential of carvone, a monoterpene abundant in cilantro and spearmint essential oils. Using an integrated network pharmacology approach combined with experimental validation, we identified 62 potential therapeutic targets. Our findings suggest that carvone may treat UC by regulating key genes (ESR1, SRC, PIK3R1, TNF) and multiple pathways, including TNF-α/NF-κB signaling, inflammation response, and cell proliferation. In a dextran sulfate sodium (DSS)-induced colitis model, carvone significantly ameliorated disease progression, as evidenced by reduced disease activity index scores, preserved body weight, maintained colon length, and improved histopathological parameters. Molecular analyses demonstrated that carvone substantially downregulated key pro-inflammatory mediators, including IL-6, IL-1β, and TNF-α, both in vivo and in vitro. Mechanistically, carvone effectively suppressed of NF-κB p65 phosphorylation and nuclear translocation, indicating its role in regulating the NF-κB signaling pathway. Additionally, high-throughput 16S-rDNA sequencing analysis revealed that while carvone treatment did not significantly alter overall gut microbiota diversity or community structure, it selectively normalized the abundance of pathogenic Bacteroides species, including B. eggerthii, B. vulgatus, and B. clarus, to levels comparable to healthy controls. These findings suggest that carvone exerts therapeutic efficacy in UC through associations with alterations in the NF-κB inflammatory signaling pathway and shifts in disease-associated gut microbiota composition. However, we acknowledge the need for further causal validation studies, such as gene-deficient cell or mouse models and fecal microbiota transplantation experiments, to fully elucidate the mechanisms underlying these effects. This highlights carvone’s potential as a novel therapeutic strategy for UC management.