The current study was directed to explore new natural products that alleviate inflammation with the least harming effects on the gastric mucosa. This study examined the anti-ulcerative properties of micro and nanocrystalline cellulose (MCC, NCC) palm frond and their chemically modified samples (sulfated (SMCC and SNCC), methylated (MMCC and MNCC) and phosphorylated (PMCC and PNCC)). The lowest prebiotic index (I) was recorded in case of the MMCC and MNCC extract with L. Reuteri (I = 1) while the higher prebiotic index was recorded in case of the PMCC against L. casei (I = 3.7). All treated groups showed significant improvements in the ulcer scores (P < 0.05) compared to the control (indomethacin) group. However, MMCC showed marked effects similar to ranitidine. A significant decrease was found in pro-inflammatory cytokines (IL-6 and TNF-α) and pro-apoptotic gene (Bax) in all treated groups compared to the ulcer-induced group. In conclusion, the histopathological evaluation of MNCC, PNCC and SNCC had superior ameliorating effect on gastric ulcer induced in rats when compared to Omeprazole 20 mg/kg and other treated groups (MMCC, PMCC, SMCC).