Combination of multiple enzymes for cascade catalysis has been widely applied in biomedicine, but integration of natural bioenzyme with inorganic nanozyme is less developed. Inspired by the abundant content of superoxide dismutase (SOD) in Spirulina platensis (SP), we establish integrated cascade catalysis for anti-inflammation therapy through decorating catalase (CAT)-biomimetic ceria nanoparticles (CeO2) onto SP surface via electrostatic interaction to build microalgae-based biohybrids. The biohybrids exhibits combined catalytical competence for preferentially transforming superoxide anion radicals (O2•−) to hydrogen peroxide (H2O2), and subsequently catalyzing H2O2 disproportionation to water and oxygen. In ulcerative colitis and Crohn’s disease, the biohybrids reveals satisfactory therapeutic effect owing to the synergistic reactive oxygen species (ROS)-scavenging capacity, proposing new train of thought for enzymes-based biomedical application.