Using theoretical calculations and Born-Oppenheimer molecular dynamics simulations, it is shown here that Criegee intermediate, which is principally produced in the olefin ozonolysis, can activate H-X (X = H, CH3, CH2F, CHF2, CF3, and SiH3) under mild conditions, a reaction that has long been known for transition metals. The zwitterionic electronic structure of Criegee intermediate makes it an interesting metal-free system for activating enthalpically strong small molecules such as H-2, methane, silanes, and boranes. The calculated barriers for the H-2 or SiB4 reactions of CH2OO are significantly lower than those for the CH4 or its fluorinated analogue reactions. The distortion interaction energy model is found to be successful in explaining the differential reactivity of the Criegee intermediate toward activating the various H-X bonds. The canonical transition state theory calculations suggest that the CH2OO-H, reaction is 9-11 orders of magnitude faster than the CH2OO-CH4 reaction over the 200-300 K temperature range. Considering that the laboratory synthesis of Criegee intermediate is now feasible, these findings may open up new vistas in the metal -free activation of small molecules.