Background: Rice bran proteins and their hydrolysates exhibit anticancer activity. Our previous study demonstrated that Riceberry glutelin and its hydrolysates possessed potent in vitro antioxidant and antimutagenic properties. However, their cancer chemopreventive effects in animals remain unclear. Methods: This study investigated chemopreventive mechanisms in diethylnitrosamine (DEN)- and 1,2-dimethylhydrazine (DMH)-induced preneoplastic lesions, including glutathione S-transferase placental form (GST-P)-positive foci in the liver and aberrant crypt foci (ACF) in the colon of rats. Rats received GTL, GTLH, and total protein hydrolysate (TPH) at 500 mg/kg body weight, five days per week for ten weeks. Results: GTLH significantly reduced GST-P-positive foci in the liver and ACF in the colon, while GTL decreased GST-P-positive foci only in the liver. However, TPH did not affect preneoplastic lesions in both the liver and the colon. GTLH suppressed cell proliferation by reducing proliferating cell nuclear antigen (PCNA)-positive cells and promoted apoptosis, as indicated by an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in both organs. GTL also decreased PCNA-positive cells in the liver and colon. Moreover, GTLH significantly upregulated BAX and CASP3 in the liver, while only BAX in the colon was observed. Conclusions: This study highlighted the cancer chemopreventive potential of Riceberry GTLH with its underlying mechanism to reduce the number of preneoplastic lesions in the liver and colon through cell proliferation inhibition and apoptosis induction. These findings suggested that this protein hydrolysate might be used as a functional food ingredient or dietary supplement for cancer prevention.