Probiotics are live microorganisms which provide numerous health benefits to host such as immunomodulation, maintaining homeostasis of gut, preventing infections, and improving diarrheal conditions. However, the emergence of novel probiotic strains from different sources with potential health benefits has increased significantly which also raises concerns on the safety of such novel strains. Bacteria with probiotic characteristics usually belong to the group of lactic acid bacteria which are categorized under “generally regarded as safe.” However, some pathogenic bacteria and host microbiota cause damage to deoxyribonucleic acid (DNA) when host-microbe homeostasis is disturbed, which can lead to colorectal cancers and cancers of epithelial cell lining. This chapter focuses on the evaluating genotoxicity of probiotic strains by mammalian erythrocyte micronucleus test on Balb/c mice.