Current studies indicated a potential inverse association between plant-based diets (PBD) and inflammatory bowel disease (IBD). Large-scale research is needed to confirm the protective role of PBD in IBD risk. This study evaluated the associations between PBD and IBD risk and explored potential mediators. This prospective cohort study included 143 434 UK Biobank participants, using 24-h dietary recalls to calculate PBD indexes. Cox regression assessed associations between PBD and IBD risk. Decomposition and mediation analyses evaluated dietary components and serum biomarkers. During a mean follow-up of 14.5 years, 1117 participants developed IBD (795 UC, 322 CD). Results showed inverse associations between hPDI and UC risk (0.92, 95% CI = 0.86-0.99) and CD risk (0.86, 95% CI = 0.77-0.96), and between PDI and CD risk (0.86, 95% CI = 0.77-0.96). A positive association was found between uPDI and CD risk (1.15, 95% CI = 1.02-1.29). Fruits and vegetables were identified as protective factors. Neutrophils, white blood cells, and CRP were major mediators of the associations between PBD and IBD risk. The healthy plant-based diet is inversely associated with IBD risk and may be partly explained by the anti-inflammatory properties of plant-based foods.