The development of colorectal cancer involves some morphological changes, and in the initial stage, pre-neoplastic lesions called aberrant crypt foci (ACF) appear. Thus, an intervention with sources of bioactive compounds such as Hibiscus sabdariffa L., rich in phenolic compounds and anthocyanins, could attenuate the risk of developing these lesions due to its antioxidant, anti-inflammatory and anti-proliferative properties. Therefore, the aim of this study was to evaluate the effects of 5% and 10% supplementation of dehydrated H. sabdariffa calyces (DHSC) during the development of 1,2-dimethylhydrazine-induced preneoplastic lesions in male BALB/c mice. The characterization of DHSC was carried out. The in vivo experiment lasted 12 weeks, and the animals were randomly divided into 3 experimental groups: the control group (CON) and the supplemented groups with 5% DHSC and 10% DHSC. The activities of liver enzymes catalase and superoxide dismutase were determined. In addition, ACF, short chain fatty acids (SCFA), presence of inflammatory infiltrates, goblet cells and leukocytes in the colonic mucosa were quantified. There was a significant reduction in ACF and the presence of inflammatory infiltrates in the colon of animals in groups 5DHSC and 10DHSC. In addition, the 10DHSC group showed an increase in the activity of the catalse enzyme, in the production of butyrate and in the presence of NK cells in the colon, in addition to more hypertrophied goblet cells. Based on these findings, it is suggested that DHSC supplementation may be recommended to attenuate cellular responses in the early stage of preneoplastic lesions.