Laboratory studies were carried out to determine the efficacy of ozone (O₃) technology as a management tool against larvae of Ephestia cautella, Plodia interpunctella, Trogoderma granarium and Tribolium castaneum. In addition, some biochemical changes and ultrastructural alterations in the above-mentioned larvae were studied. Larval mortality of the four species increased as concentration and exposure periods increased. Complete mortality was observed after 8 h. The LT_50–99 values of ozone gas against the larvae decreased as concentration increased. Caterpillars were more sensitive to O3 than grubs. Data also showed that the effective effect of ozonation towards the four larval species indicated that not all insects had the same sensitivity to ozone gas. There was a significant increase in super oxide dismutase (SOD) levels in E. cautella and T. castaneum subjected to LT₅₀ of ozone. Moreover, there was a significant decrease in nitric oxide concentration in both larvae after LT₅₀ of ozone exposure. Ozone-treated larvae suffered from heterogeneous muscles with degenerated nuclei. The neurosecretory cells were found with accumulated neurosecretory materials. The neuropil glia appeared loose and vacuolated. Antenna appeared with loose sinus, and there were no artery nor trachea found. The mushroom body of brain calyces appeared with distributed Kenyon cells. The cuticular layer was degenerated. The tracheae were collapsed. Thus, ozone gas may be used as a clean and safe agent to fight these pests.