As people spend a greater portion of their time indoors, the likelihood of exposure to biohazards in indoor air is increasing. This study developed a system to disinfect indoor bioaerosols while protecting occupants from direct exposure to ozone. This hybrid approach combines high concentrations of ozone generated by a non-thermal dielectric barrier discharge system, and an ozone decomposition unit using MnO2/Al2O3 and MnO2/AC catalysts. Four types of common bioaerosols were used to test the germicidal efficacy of 0–175 ppm ozone at a relative humidity of 30–70% and retention time of 1–10 s. The results indicate that the germicidal efficacy of ozone on E. coli, C. famata and P. citrinum spore bioaerosols increased with ozone concentration, relative humidity, and retention time; however, the process was less effective with the hardy endospores of B. subtilis. Germicidal efficacy of 90% was obtained for bioaerosols (two vegetative cells and one spore) using high concentrations of ozone at a relative humidity of 70% and exposure time of 10 s. Residual ozone in the tail gas was decomposed to undetectable levels using catalysts at a gas hourly space velocity of 3.287 × 103 1/h. The concentration of indoor bioaerosols (total bacteria and fungi) in a small office was reduced to below 50 CFU/m3 and ozone in the tail gas was reduced to undetectable levels following treatment for 2 h. The hybrid system of ozone disinfection and catalysts provides high germicidal efficacy while protecting occupants from direct exposure to ozone.