Coextrusion technologies are commonly used to produce multilayered composite sheets or films for a large range of applications from food packaging to optics. The contrast of rheological properties between layers can lead to interfacial instabilities. Important theoretical and experimental advances regarding theses defects have, during the last decades, been made using a mechanical and numerical approach. This study deals with the influence of the physicochemical affinity between the neighboring layers on interfacial instabilities for functionalized incompatible polymers. It was experimentally confirmed, in this case, that weak disturbance can be predicted by considering an interface of nonzero thickness (corresponding to an interdiffusion/ reaction zone interphase) instead of a purely geometrical interface between the two reactive layers. According to the rheological investigations, an experimental strategy was here formulated to investigate the parameters that controlled the stability of the reactive multilayer flows. The role of the viscosity ratio, elasticity ratio, and layer ratio of the stability of the interface was also investigated coupling to the reaction rate/ compatibilization phenomenon. Hence, based on this analysis, guidelines for a stable coextrusion of reactive functionalized polymers can be provided coupling the classical parameters and the physicochemical affinity at the polymer/polymer interface