The purpose of this experiment was to examine the therapeutic effect of the ethanolic extract from Gynura procumbens against ulcerative colitis. In this experiment, BALB/c male mice and SD male rats were used to establish animal models with mild and severe ulcerative colitis, respectively, through intraintestinal administration of TNBS-50% ethanol solution. Then, different doses of Gynura procumbens extract and its effective components (alone or in combination) were administered separately, and H&E and PAS staining techniques were used to evaluate colonic injury-related pathological changes. The results showed that compared with the mild ulcerative colitis model group, the glycogen content of the low-dose and high-dose Gynura procumbens group decreased by 147.14% and 178.89%, respectively, with the goblet cell content of these two groups increased by 15.39% and 36.77%. Compared with the severe ulcerative colitis model group, the glycogen content of Gynura procumbens group increased by 45.00% with the goblet cells increasing by 95.62%. The Gynura procumbens extract can be used to treat mild and severe ulcerative colitis as a potential drug for further development.