Chirality is a fundamental property of a molecule, and the significant progress in chirality detection and quantification of a molecule has inspired major advances in various fields ranging from chemistry, biology, to biotechnology and pharmacology. Chiral molecules have identical molecular formulas, atom-to-atom linkages, and bonding distances, and as such they are difficult to distinguish both sensitively and selectively. Today, most new drugs and those under development are chiral, which requires technological developments in the separation and detection of chiral molecules. Therefore, rapid and facile methods to detect and discriminate chiral compounds are necessary to accelerate advances in many research fields. The challenges in analysis stem from the obvious fact that chiral molecules have the same physical properties. Although significant progress on the detection of enantiomeric composition has been achieved in the past decade, in order to fully realize the capacity of chiral molecular interrogation, highly sensitive and selective, portable, and easy-to-use detection remains challenging because of the limitation of conventional techniques.Soft nanoarchitectonics is a new concept for the fabrication of functional soft material systems through harmonization of various actions including atomic/molecular-level manipulation, chemical reactions, self-assembly and self-organization, and their modulation by external fields/stimuli. Soft nanoarchitectonics has been widely used as a key enabling technology for integrating predefined molecular functionalities including electrochemical, optical, catalytic, or biological properties into biosensing devices, which provides exciting opportunities to design, assemble, and fabricate tailored nanosystems to enable new sensing strategies for chiral molecules.In this Account, we aim to concisely discuss how these molecule-inspired soft nanoarchitectonics work for enantioselective sensing. We will first outline the basic principle and mechanistic insights of the soft nanoarchitectonics approach for enantioselective sensing, and then we will describe the new breakthroughs and trends in the area that have been most recently reported by our groups and others. There will also be a discussion on the merits of soft nanoarchitectonics based sensing in comparison to conventional analytical methods. Finally, with this Account, we hope to spark new chiral molecule sensing strategies by fundamentally understanding chiral recognition and engineering soft nanoarchitectonics with programmable structures and predictable sensing properties.