Ambidextrous supergelators are developed through structure-gelation screening of rationally designed cyclic dipeptides (CDPs). The organo- and hydrogels of CDPs were thoroughly characterized by their minimal gelation concentration (MGC) for organic and aqueous solvents, thermal stability (T-g), and viscoelastic properties. Intermo-lecular hydrogen bonding, the major driving force for gelation was evaluated using temperature-dependent nuclear magnetic resonance (NMR) spectroscopy. The contribution of attractive van der Waals interaction of tBoc group in driving CDP gelation was ascertained using beta-cyclodextrin (beta-CD)-adamantane carboxylic acid (AC)-based host guest gelation and H-1 NMR. studies. The self-assembled fibrous network of CDPs in organic and aqueous solvents responsible for the molecular gelation was elucidated using field emission scanning electron microscopy (FESEM) analysis. Among the CDPs studied CDP-2 found to be supergelator with MGC of 0.3 wt % and form in situ hydrogels under simulated physiological conditions. The in situ gelation property was evaluated by the incorporation of curcumin, as a model study to demonstrate the drug delivery application. Furthermore, supergelator CDP-2 was found to exhibit in cellulo cytocompatibility. Moreover, density functional theory (DFT) calculations were carried out to propose the microscopic structure for the self-assembly of CDP compounds and intermolecular N-H center dot center dot center dot O hydrogen bonding interactions appear to stabilize the fibrous network. The hydrophobic interactions among the tert-butyloxycarbonyl (tBoc) groups and pi-pi stacking interactions between phenyl rings contribute to the further stabilization of self-assembled 2D fibrous networks of CDPs. Overall, the present study highlights the in situ gelation property of CDP-based supergelators and their potential for biomedical and regenerative medicine applications.