The Amazon region harbors one of the richest biodiversities on the planet, representing a vast reservoir of bioactive compounds with high therapeutic potential. Although several Amazonian bioactives have already been incorporated into biopolymeric matrices, the effects of their incorporation on the mechanical, barrier, and biological properties of these materials remain insufficiently systematized. This review addresses this knowledge gap by critically analyzing reported Amazonian bioactive–biopolymer systems, with emphasis on how bioactive incorporation influences matrix properties, release behavior, and biological performance, particularly in biomedical applications. Emphasis is placed on the role of polymer–bioactive interactions in modulating physicochemical, mechanical, and transport properties, as well as in controlling release kinetics and biological performance. Different incorporation strategies, such as encapsulation and matrix embedding, are critically discussed in terms of their impact on stability and functionality. Overall, the reported studies demonstrate that Amazonian bioactives can substantially modulate the physicochemical, mechanical, barrier, and biological performance of biopolymeric systems, depending on the bioactive, polymeric matrix, and incorporation strategy. However, challenges related to variability in raw materials, lack of standardization, and limited reproducibility remain key barriers to translation and large-scale application.