Aim: To evaluate the ability of red and white hibiscus (H) in improving the epithelial barrier in indomethacin-induced duodenal and colonic inflammation, compared with prebiotic and to investigate whether the red and/or white hibiscus can be used as natural prebiotic like agents. Methods: Histological, histomorphometric, histochemical demonstration for goblets cells and mucin intensity. Immunohistochemical demonstration of COX-2, and tight junctions (Claudin-1 and E-cadherin) were examined. Duodenal and colonic TNF-α, IL-6, IL-10, PGE2, MPO, MDA, TAC, besides, serum CRP were evaluated. Results: Indomethacin induced inflammation and ulceration in the duodenum and colon, with significant depletion in goblet cell count and mucin intensity. COX-2 was increased while claudin-1 and E-cadherin were significantly diminished. Tissue TNF-α, IL-6, MPO, MDA, and serum CRP were elevated significantly by indomethacin, while IL-10, PGE2 and TAC were reduced. Co-treatment with red H, white H, or prebiotics plus indomethacin improved significantly duodenal and colonic histoarchitecture, tissue contents of PAS cells, mucin, claudin-1 and E-cadherin, while COX-2 reduced. TNF-α, IL-6, MPO, MDA, and serum CRP were decreased significantly, while IL-10 , PGE2 and TAC were restored. Conclusion: The current research introduces red and white hibiscus as prebiotics-like agents because of their anti-inflammatory, antioxidant, or tight junctions modulating activities.