The rich electronic and band structures of monolayered crystals offer versatile physical/chemical properties and subsequently a wide range of applications. Fabrication, particularly by the top-down “exfoliation” processes, relies on the presence of weak van der Waals force between individual layers. Due to the strong chemical bonds between planes and atoms, unzipping ultrathin crystals (from one to several unit cells thick) from non-layered structures is more challenging. This work reports a technique used to prepare such ultrathin crystals from bulk non-layered structures (ɑ-/β-MnO2, ZnO, TiO2, ɑ-TiB2). The physical and optical properties of these materials are characterized and contrasted against those from their bulk phases. The work presented here represents a tool kit for the preparation of novel 2D non-layered nanomaterials, providing significant contributions to this family of materials, paving the way for even more applications. Furthermore, we show the application of these novel NCs for biosensing and electrochemical oxygen reduction. 2D non-layered interfaces are expected with many unusual properties which depend on not only the exposure facet, crystal phase, but also the other surface arrangement at atomic level. The formation of ultrathin 2D non-layered nanostructures, from one to several unit cells thick, could offer a way to use these novel interfaces for various applications. However, direct growth of these ultrathin structures is difficult, while the exfoliations from bulk raw materials are also highly challenging due to the strong chemical bond between unit cells and atoms. Therefore, we develop the “K-insertion and unzipping” technique in this work to unzip the chemical bond, ranging from covalent to ionic and metallic bonds, of the bulk non-layered structures. This allows us to form 2D ultrathin structures, providing an avenue for various novel 2D non-layered materials, interfaces, and associated applications. This study provides a technique to unzip chemical bonds of bulk non-layered structures to form ultrathin 2D nanocrystals from one to several unit cells thick, give rise to novel properties, providing a toolbox to enable various implementations of such non-layered 2D nanostructures from bioscience to electrocatalysis.