Bio-based polyamides (100%) with responsive functionality were designed and synthesized by using biorenewable diamine and dicarboxylate. 1,5-Pentanediamine and dimethyl furan-2,5-dicarboxylate were chosen not only because of the biomass feedstock but also because of the reactivity of the furan rings. Enzymatic process enhanced the sustainability of these 100% bio-based furan-containing polyamides (PASF). By regulating the temperature, PASF was cross-linked at a low temperature via the Diels-Alder (DA) reaction and then was de-cross-linked at a high temperature. Alternatively, ultrasound exhibited a better performance in triggering the transformation of cross-linked polymers back to the original ones. The DA linkage could also be solidified by aromatization. The thermal properties were well controlled by reversible cross-linking. These 100% bio-based polyamides would open the window for the development of smart sustainable polymers with broad applications.