This paper reports the novel synthesis of 5′-CMP molecule-mediated pH-responsive porous supramolecular hydrogels consisting of β-FeOOH/5′-CMP core-shell type nanohybrids as building blocks. The as-synthesized hydrogels have been fully characterized in terms of the size of the core and shape/morphology along with their optical, magnetic and rheological features. Interestingly, the gelation in the self-assembly is induced by the puckering of ribose sugar in the 5′-CMP molecule enhancing the intermolecular non-covalent interactions between 5′-CMP of different nanohybrids as well as β-FeOOH in a relatively narrow pH (5.5-7; 7-8.5) and temperature (35-40 °C) range. These changes have been analyzed by IR, Raman and CD spectroscopy. The viscoelastic nature of the optimized sample is revealed by fairly high values of viscosity (5.56 × 103 cP), G′ (4 × 104 Pa), G′′ (2.3 × 102 Pa) and yield strain (8.1%) with a linear viscoelastic region up to about 4%. A decrease in viscosity with shear rate demonstrates its gel like behavior matching with that of soft supramolecular hydrogels. The mechanism of gel formation has been thoroughly analyzed. pH, temperature and mechanical force induced spontaneous transition(s) of the sol into a hydrogel and its complete reversal into the sol suggest it to be a smart material. Thus, the soft hydrogels consisting of greener components such as a pyrimidine nucleotide (5′-CMP) and β-FeOOH phase, synthesized under physiological conditions of pH (7) and temperature (37 °C) with fairly high surface area, exhibited self-healing properties, injectability, relatively higher %swelling (530), and efficient loading (217 mg g-1) and release of adsorbed methylene blue (>98%; model drug) over a period of more than 3 days in aqueous PBS buffer, suggesting them to be sustainable with significant potential in biological and environmental applications. © 2019 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.