Goji berry and mulberry are both popular berries with anti-colitis effects, but their leaves have received less attention. In this study, the anti-colitis effects of goji berry leaf and mulberry leaf were investigated in dextran-sulfate-sodium-induced colitis C57BL/6N mice compared with their fruits. Goji berry leaf and goji berry reduced colitic symptoms and ameliorated tissue damage, while mulberry leaf did not. ELISA and western blotting analysis suggested that goji berry showed the best performance in inhibiting the overproduction of pro-inflammatory cytokines (TNF-α, IL-6 and IL-10) and improving damaged colonic barrier (occludin and claudin-1). Besides, goji berry leaf and goji berry reversed the gut microbiota dysbiosis by increasing the abundance of beneficial bacteria like Bifidobacterium and Muribaculaceae, and decreasing the abundance of harmful bacteria like Bilophila and Lachnoclostridium. Goji berry, mulberry and goji berry leaf could restore acetate, propionate, butyrate and valerate to ameliorate inflammation, while mulberry leaf could not restore butyrate. To the best of our knowledge, this is the first report on the comparison of the anti-colitis effects of goji berry leaf, mulberry leaf and their fruits, which is meaningful for the rational utilization of goji berry leaf as a functional food.