Inflammatory bowel disease (IBD) is a refractory chronic intestinal disease caused by immune dysfunction, with an unknown pathogenesis. In this study, the peptide GTSFTTTAER was isolated from Rapana venosa for treatment of IBD for the first time. We examined its protective effects on a zebrafish model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced IBD. The results indicate that the peptide GTSFTTTAER ameliorates intestinal inflammatory injury by reducing the number of immune cells at the intestinal site and increasing the frequency of intestinal peristalsis. Besides, in order to predict and verify the potential mechanism of the anti-inflammatory effects of peptide GTSFTTTAER, we performed transcriptome and reverse transcription-quantitative polymerase chain reaction analysis. The transcriptome analysis revealed that the key pathways for the potential protective effects of GTSFTTTAER were the Toll-like receptor signaling pathway and the necroptosis pathway. Lastly, molecular docking technology further confirmed the action target of peptide GTSFTTTAER. In conclusion, GTSFTTTAER has a beneficial effect on IBD in TNBS-induced zebrafish. Our study will provide a valuable reference for the utilization of peptide GTSFTTTAER from Rapana venosa, and it may also be helpful in developing therapeutic agents for IBD.