Background Colorectal cancer (CRC) is one of the most common causes of cancer death in the world. Although genes are considered the most importantcauses that contribute to CRC, the intestinal microorganisms are an important player. Recently, various studies ensured the role of microbial infection and the ensuing inflammation in colon cancer initiation and progression. This present study tries to introduce a cheap nano-peroxidase (an antioxidant enzyme) produced from natural sources as efficient and safe antibacterial and anti-inflammatory agent against bacteria and inflammation related to colorectal cancer. Methods Silica nanoparticles were prepared from rice straw. Peroxidase extracted from the dry onion scales was then immobilized on the prepared nanosilica (nano-peroxidase). The antibacterial activity of the prepared nano-peroxidase was tested against the four horsemen bacteria in CRC, Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, and Salmonella enterica. The in vitro anti-inflammatory activity of the prepared nano-peroxidase also tests through performing inhibition of albumin denaturation test. Results The prepared nano-peroxidase showed high antibacterial activity against the tested bacteria in presence of very low concentration of H2O2. Immobilization increased the peroxidase stability and protected it from hydrolysis enzymes produced by the bacteria. The prepared nano-peroxidase interestingly showed significant higher anti-inflammatory activity than that of the standard (Aspirin). Conclusion Nano-peroxidase can be considered a promising safe anti-inflammatory and antibacterial agent against bacteria and inflammation related to colorectal cancer.