BackgroundPlant-Derived Exosome-Like nanoparticles (PELNs) are vital bioactive vesicles from medicinal plants, containing protective flavonoids, polyphenols, alkaloids, terpenoids, saponins, polysaccharides, and microRNAs. These compounds play crucial roles in PELNs’ anti-inflammatory and other pharmacological effects. PELNs show promise as a treatment in animal experiments for ulcerative colitis (UC) due to their biocompatibility, low immunogenicity, and natural targeting abilities. This review examines their therapeutic effects on UC and the potential mechanisms behind their action.MethodsThis study synthesises existing data through a meta-analysis, providing comprehensive preclinical evidence for the use of PELNs in ulcerative colitis. To identify studies examining the effects of PELNs on UC, the researchers conducted a comprehensive search of five databases.ResultsThis search identified a total of 25 eligible studies involving 304 animal subjects, with data up to 15 September 2025. According to the results of the meta-analysis, PELNs demonstrated significant effects in mitigating weight loss, increasing colon length, and reducing faecal consistency scores. Further mechanistic studies suggest that PELNs may exert their effects through multiple pathways. In addition to influencing inflammatory factors and the mucosal barrier, PELNs may also modulate the microbiota during the repair process of UC. PELNs intervention resulted in a statistically significant change in the Chao index (p = 0.05) and a highly significant change in the Shannon index (p < 0.0001).ConclusionThis meta-analysis suggests that, in animal models of ulcerative colitis (UC), PELNs may be associated with antioxidant, anti-inflammatory, immunomodulatory and intestinal barrier-protective effects. This study only supports the correlational results derived from preclinical animal studies, and cannot confirm the definite action mechanisms nor clinical efficacy in humans. Further basic researches are still needed for in-depth exploration. Visit https://inplasy.com/inplasy-2025-11-0075/ to access the systematic review registration, labeled as INPLASY2025110075.Systematic Review RegistrationIdentifier INPLASY2025110075.