Substrate-assisted product desorption often proposed in heterogeneous catalysis (nanozymes) denounces the catalytic deactivation of heterogenous catalysts. On contrary, the catalytic deactivation of rigid heterogeneous catalysts becomes noticeable in a continuous flow reactor. Surprisingly, it has been addressed inadequately and in an isolated manner. In this study, we have developed a cost-effective non-lithographic method for fabrication of PDMS-based microchannel-coupled-millireactor. Immobilized Nickel particles are resistant to leaching in flow process. During continuous operation, millireactors show strong catalytic activity for reduction of resazurin andp-nitrophenol with a conversion rate of almost 100%. The catalytic poisoning is ubiquitous and being gradually prominent whereas complete catalytic deactivation of magnetic Ni-microparticle is found to be an instantaneous process. Relatively larger-sized resorufin binds predominantly to the surface and thereby blocks the access of substrate to Ni-particle. The dissociations of product molecules - resorufin and p-aminophenol are the rate-limiting steps that caused the abrupt deactivation of Ni-microparticle. The kinetic mechanism of heterogeneous derived from the Langmuir-Hinshelwood mechanism satisfactorily explain the catalytic poisoning and deactivation of Nickel microparticle. This study sheds light on the intricacies of catalytic activity and poisoning of magnetic Nickel microparticles.