By the means of a series of simulation approaches and experimental investigations, we explore the acceleration phenomenon (i.e., catalysis) of a Diels-Alder (DA) reaction between cyclopentadiene and acrylonitrile in water microdroplets. Quantum-mechanical calculations and first-principles molecular dynamics coupled with enhanced sampling techniques revealed that the partial solvation effect and local interfacial electric field at the water microdroplet surface are not factors accelerating the DA reaction. Specifically, the free-energy barrier of the DA reaction at the water microdroplet interface was found to be approximately 1 kcal/mol higher compared to the bulk phase one. Although the presence of a local strong electric field at the gas-liquid interface could slightly decrease the barrier by about 2 kcal/mol along the reaction axis, the fluctuating nature of this interfacial electric field significantly inhibits its catalytic effect on the DA reaction. These predictions were confirmed by microdroplet experiments.