Microwave (MW) and enzyme catalysis are two emerging processing tools in the field of food industry. Recently, MW has been widely utilized as a novel type of green and safe heating energy. However, the effect of MW irradiation on enzyme activity is not described clearly. The intrinsic mechanisms behind enzyme activation and inactivation remain obscure. To apply better MW to the field of enzyme catalysis, it is essential to gain insights into the mechanism of MW action on enzyme activity. This review summarizes the changes in various enzyme activity during food processing, especially under MW irradiation. The intrinsic mechanism of thermal and nonthermal effects of MW irradiation was analyzed from the perspective of enzyme reaction kinetics and spatial structure. MW irradiation temperature is a vital parameter affecting the catalytic activity of enzymes. Activation of the enzyme activity is achieved even at high MW power NOMENCLATURE/ABBREVIATIONS: A, frequency factor (-); APX, ascorbate peroxidase; CALB ex 10000 LA, Candida antarctica lipase B expressed in yeast cells; CAT, catalase; Cat L, cathepsin L; CTH, conventional heating; D R (D 1 ) and D L (D 2 ), the time required for inactivation of 90% of the activity of the thermosensitive and thermoresistant fractions, respectively (s); D w , the time for the first decimal reduction (s); D w , ref , the time for the first decimal reduction at T ref (s); E a , energy of activation (J/mol); Fermase CALB10,000, Candida antarctica lipase B immobilized on microporous and hydrophobic polyacrylate beads using covalent binding; k, rate constant (min −1 ); k R (k 1 ) and k L (k 2 ), the inactivation rate constants for heat-resistant and heat-labile enzyme fractions, respectively (s −1 ); LA, lipase activity; LA QLM, thermophilic lipase QLM from Alcaligenes sp.; MWH, microwave heating; Novozym 435, Candida antarctica lipase B immobilized using an acrylic resin support; POD, peroxidase; PPO, polyphenol oxidase; SOD, superoxide dismutase; TG, transglutaminase; T ref , equivalent isothermal processing time at a given reference temperature ( • C); z w , the temperature increase that reduces D w by 90% ( • C); β, the shape parameter of the Weibull distribution (-); ΔG, Gibbs free energy (kJ/mol); ΔH, enthalpy change (kJ/mol); ΔS, entropy change (kJ/mol/K); δ T , the time for the first decimal reduction at a given temperature T (s).Hongwei Cao and Xiaoxue Wang contributed equally to this work.