In order to effectively deliver lutein to the inflamed colon and better exert its pharmacological activity, this paper constructed a sodium alginate hydrogel-based delivery system loaded with lutein nanoparticles, evaluated the regulation on the expression and secretion of related inflammatory factors in mice with colitis, and its impact on intestinal microbial environment. The results showed that comparing lutein crystal and its nanoparticle, lutein hydrogel alleviated dextran sodium sulfate (DSS)-induced colitis in mice more effectively by adjusting fecal heme content, colon tissue damage, and inflammatory factor levels. Moreover, lutein hydrogel increased the expression of intestinal tight junction proteins zonula occluden-1 (ZO-1), claudin-1 and occludin to maintain the integrity of the intestinal-barrier, inhibited the nuclear factor-κB (NF-κB) pathway and reduced expression and secretion of inflammatory factors including tumour necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), NOD-like receptors 3 (NLRP3) and interleukin (IL)-1β. In addition, the intestinal microbial environment of mice with colitis was improved by down-regulating the relative abundance of Desulfovibrionaceae and up-regulating the relative abundance of Erysipelotrichaceae and Rikenellaceae. As a slow-release carrier to load lutein nanoparticles, sodium alginate-based hydrogel has potential application prospect.