<p>Chiral mechanically interlocked molecules provide a promising platform for enantioselective recognition and asymmetric catalysis, enabled by their unique combination of topological complexity and stereochemical control. Despite recent advances, the rational construction of higher-order chiral interlocked architectures such as molecular knots and links remains a synthetic challenge. Moreover, the influence of molecular chirality on the formation of such topological structures, and the resulting functional consequences, has been largely unexplored. Here we report an amino-acid-encoded assembly strategy as a general approach for the synthesis of programmable Solomon links (doubly interlocked [2]catenanes) featuring multiple levels of structural chirality. By leveraging the stereochemical configurations of amino acids to introduce chiral bias and encode structural information, we demonstrate that the assembly process preferentially follows a homochiral assembly pathway over non-chiral or heterochiral alternatives, resulting in a library of chiral Solomon links with tunable cavity size and shape, generated in a single step with high efficiency. These interlocked molecules exhibit exceptional chiral amplification (∼350-fold increase) and outstanding binding affinity and enantioselectivity for peptides, with practical applications in interleukin-6 detection (∼12 nM sensitivity). This template-free synthetic approach paves the way to the custom design of chiral interlocked architectures and materials with tailored properties.</p><p></p>