This study isolated and characterized a novel lytic bacteriophage (vB_BceS-M2) active against toxigenic and multidrug-resistant Bacillus cereus and evaluated its antibacterial efficacy alone and in combination with the antimicrobial peptide nisin. The phage exhibited broad host range, high stability across a wide range of temperatures and pH values, and its genome lacked virulence, lysogeny, and antibiotic resistance genes. Checkerboard analysis demonstrated a strong synergistic interaction between phage and nisin, resulting in enhanced bacterial inactivation and suppression of phage-resistant cells. The combined treatment was also effective in multiple food matrices, including milk, boiled rice, cheese, and frozen meatballs, highlighting its potential as a safe and natural strategy for controlling multidrug-resistant Bacillus cereus and improving food safety.