Background: Aerial parts of Malva nicaeensis All. are preferred in the prevention and treatment of intestinal infections and hemorrhoids in Turkish traditional medicine. This study is planned to evaluate the pharmacological activity of M. nicaeensis extracts on rats with acetic acid-induced colitis. Methods: The plant material was subsequently extracted with n-hexane, ethanol, and water, respectively. All of these extracts were tested for efficacy in the acetic acid-induced rat colitis model. The aqueous and polysaccharide extracts regulated cytokine levels and antioxidant parameters. Furthermore, the aqueous extract in particular regulated myeloperoxidase and caspase-3 levels in this rat model. In addition, the polysaccharide-rich fraction was separated from the aqueous extract. Results: The polysaccharide-rich fraction and aqueous extract regulated cytokine levels and antioxidant parameters. The aqueous extract also positively affected myeloperoxidase and caspase-3 levels. The phytochemical studies revealed that the aqueous extract had the highest phenolic content. In addition, the polysaccharide fraction was found to contain total sugars, sulfated groups, uronic acids, and total proteins in 78.4%, 0.9%, 1.5%, and 14.7%, respectively, and was rich in monosaccharide-type compounds, especially galactose (36.4%). Conclusions: M. nicaeensis was discovered to be a drug lead in the future treatment of irritable bowel diseases or as a complementary therapeutic agent that aided conventional treatments.