IL-1beta is an important cytokine implicated in the progression of inflammatory bowel disease (IBD) and intestinal barrier dysfunction. The polyphenolic compound, geraniin, possesses bioactive properties, such as antitumor, antioxidant, anti-inflammatory, antihypertensive, and antiviral activities; however, its IL-1beta-targeted anticolitis activity remains unclear. Here, we evaluated the inhibitory effect of geraniin in IL-1beta-stimulated Caco-2 cells and a dextran sulfate sodium (DSS)-induced colitis mouse model. Geraniin blocked the interaction between IL-1beta and IL-1R by directly binding to IL-1beta and inhibited the IL-1beta activity. It suppressed IL-1beta-induced intestinal tight junction damage in human Caco-2 cells by inhibiting IL-1beta-mediated MAPK, NF-kB, and MLC activation. Moreover, geraniin administration effectively reduced colitis symptoms and attenuated intestinal barrier injury in mice by suppressing elevated intestinal permeability and restoring tight junction protein expression through the inhibition of MAPK, NF-kB, and MLC activation. Thus, geraniin exhibits anti-IL-1beta activity and anticolitis effect by hindering the IL-1beta and IL-1R interaction and may be a promising therapeutic anti-IL-1beta agent for IBD treatment.