Inexperienced and nano-structured catalytic media are very important for bio-catalysis to attenuate the denaturation tendency of biocatalysts underneath extreme response situations. Hydrotropes with multi-faceted physiochemical properties signify promising techniques for sustainable protein packaging. Herein, the suitability of adenosine-5’-triphosphate (ATP) and cholinium salicylate ([Cho][Sal]) ionic liquid (IL) to type nano-structures and to nano-confine Cytochrome c (Cyt c) have been demonstrated to boost the soundness and exercise underneath a number of stressors. Experimental and computational analyses have been under-taken to elucidate the nano-structured phenomenon of ATP and IL, structural organizations of nano-confined Cyt c, and site-specific interactions that stabilize the protein construction. Each ATP and IL type nano-structures in aqueous media and will cage Cyt c by way of a number of nonspecific mushy interactions. Remarkably, the engineered molecular nano-cages of ATP (5-10 mM), IL (300 mg/mL), and ATP+IL surrounding Cyt c resulted in 9-to-72-fold greater peroxidase exercise than native Cyt c with exceptionally excessive thermal tolerance (110oC). The polar interactions with the cardiolipin binding website of Cyt c, mediated by hydrotropes, have been nicely correlated with the elevated peroxidase exercise. Moreover, greater exercise tendencies have been noticed within the presence of urea, GuHCl, and trypsin with none protein degradation. Particular binding of hydrotropes in extremely cell areas of Cyt c (Ω 40-54 residues) and enhanced H-bonding with Lys and Arg supplied excel-lent stability underneath excessive situations. Moreover, ATP successfully counteracted reactive oxygen species (ROS)-induced denaturation of Cyt c, which was enhanced by the [Sal] counterpart of IL. Total, this research explored the robustness of nano-structured hydrotropes to have the next potential for protein packaging with improved stability and exercise underneath excessive situations. Thus, the current work highlights a novel technique for real-time industrial bio-catalysis to guard mitochondrial cells from ROS-instigated apoptosis.