Inflammatory bowel disease (IBD) represents a group of intestinal disorders with self-destructive and chronic inflammation in the digestive tract, requiring long-term medications. However, as many side effects and drug resistance are frequently encountered, safer and more effective agents for IBD treatment are urgently needed. Over the past few decades, a variety of natural alkaloids made of plants or medicinal herbs have attracted considerable interest because of the excellent antioxidant and anti-inflammatory properties; additionally, these alkaloids have been reported to reduce the colonic inflammation and damage in a range of colitic models. In this review paper, we summarize the recent findings regarding the anti-colitis activity of plant-derived alkaloids and emphasize their therapeutic potential for the treatment of IBD; obvious improvement of the colonic oxidative and pro-inflammatory status, significant preservation of the epithelial barrier function and positive modulation of the gut microbiota are the underlying mechanisms for the plant-derived alkaloids to treat IBD. Further clinical trials and preclinical studies to unravel the molecular mechanism are essential to promote the clinical translation of plant-derived alkaloids for IBD.