Background: Phytochemicals with strong antioxidant and anti-inflammatory properties are known to modulate the process of carcinogenesis. Althea rosea (AR) is an ornamental plant and is an integral part of traditional medicine for curing a wide range of inflammatory disorders such as asthma, inflammatory bowel diseases, and arthritis. Therefore, its potential as a chemopreventive agent in cancer needs to be evaluated using an appropriate animal model. Materials and Methods: In this study, different in vitro assays including total phenolic content, 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate), and ferric reducing antioxidant power were used to evaluate the antioxidant capacity of AR seed extract. In addition, in vivo study at two different doses, i.e., 100 and 200 mg/kg body weight, was also conducted to analyze the chemopreventive potential of AR seed extract. The chemopreventive efficacy of AR seed extract was assessed by analysis of aberrant crypt foci (ACF), goblet cells/crypt, apoptotic index, and nuclear factor-kappa B (NF-κB) signaling pathway. Results: The results of in vitro assays suggested that AR seed extract exhibits a strong antioxidant potential. Administration of AR seed extract to 1,2-dimethylhydrazine group animals resulted in a marked reduction in ACF number, lymphocytic infiltration, and erosion of mucin layer from the intestinal epithelium. AR seed extract induced apoptosis in colonocytes as evident from the analysis of cleaved caspase-3, Bcl-2, and poly (ADP-ribose) polymerase 1/2 expression. Furthermore, treatment with AR seed extract inhibited the expression of NF-κB, a central mediator of chronic inflammation. The AR seed extract also ameliorated the damaging effects of oxidative stress by decreasing free radical generation and increasing the levels of enzymatic and non-enzymatic antioxidants. Conclusion: Taken together, these findings emphasized that AR seed extract could be considered as promising natural chemopreventive against colon carcinogenesis and should be further evaluated for the identification of active principle(s).