To analyze the phytochemical constituents, and to explore potential protective effect of the methanol extract of Moringa oleifera (M. oleifera) seeds and Egyptian propolis, each alone or concurrently administered on acetic acid-induced ulcerative colitis in rats. Methods: Eight groups of 5 rats each were used: normal control group with distilled water, model group, two groups with M. oleifera seeds (100 and 200 mg/kg), two groups with propolis (50 and 100 mg/kg), one group with concurrent administration of both, and one group with prednisolone (reference drug). Macro-and microscopic picture, ulcer index and lesion scores, oxidative markers, inflammatory mediators, in vitro activity of the inflammatory enzymes and 1, 1-diphenyl-2-picrylhydrazyl free radicals scavenging activity were evaluated. The phytochemical constituents of both extracts were explored by GC-MS analysis. Results: Both treatments modulated the macro-and microscopic picture, decreased the ulcerative index, lesion score, oxidative markers and inflammatory mediators, and inhibited the COX-1 and COX-2 enzymes. Propolis appeared to be powerful free radicals scavenger. A powerful synergistic effect of both treatments in modulating the course of the disease was reported. GCMS analysis of methanol extract of M. oleifera seeds and propolis revealed the presence of 50 and 34 compounds, respectively. Conclusions: M.oleifera seeds and propolis methanol extracts have modulated the course of acetic acid-induced ulcerative colitis. Moreover, both treatments induce a good synergistic effect against the disease. Isolation of the active constituents is recommended.