Annona squamosa belongs to the Annonaceae family, popularly known as custard apple or sugar apple. The antioxidant and chemopreventive potential of custard apple seed flours from the film (CSFF) and almond (CSAF) parts were evaluated. Total phenolic content (TPC) and total flavonoid content (TFC) were determined in the custard apple seed flours using spectrophotometric methods. The phenolic acids: gallic, caffeic, chlorogenic, p-coumaric and ferulic; catechin, epicatechin, rutin, myricetin and quercetin were analyzed by Ultra-Performance Liquid Chromatography (UPLC) with diode array detector. The antioxidant activity (ABTS) in CSFF was 73.24 µmol TE/g, and in CSAF was 4.21 µmol TE/g. CSFF had TPC of 2.59 mg GAE/g and TFC of 2.43 mg CE/g, with predominance of p-Coumaric acid (229.93 µg/g). In the other hand, CSAF presented low TPC (0.57 mg GAE/g) and TFC (0.24 mg CE/g) with no one detected phenolic compound investigated by UPLC-DAD analysis. The chemopreventive activity of feed supplemented with CSFF and CSAF (3.5, 14, and 28 mg/kg/bw/day) against DNA damage induced by doxorubicin (DXR) [20 mg/kg body weight (bw)]) was evaluated in Swiss mice peripheral blood by micronucleus test. Food and water consumption and animal weight as well as blood glucose levels were monitored during 14 days of treatment. The results showed that CSFF and CSAF exhibited no significant cytotoxic and mutagenic effects. CSFF demonstrated the greatest chemopreventive potential at the doses tested, with similar dose effect thought. In CSAF, an antimutagenic effect was observed at doses of 3.5 and 14 mg/Kg/bw/day. The interference of high phenolics compounds with antioxidant activity presented in the CSFF (e.g., coumaric acid), may explain the best protective effect against DNA damage. However, both CSFF and CSAF can be considered potential food products that could be applied in food preparations to provide antimutagenic effects.