Even today, talking about sexual dysfunction largely remains a taboo. Therefore less studies have been recorded and fewer remedies given. Erectile dysfunction (ED) is one of the most commonly treated psychological disorders that leads to major distress, interpersonal limitation and reduces the quality of life and marriage. This study aimed to assess a plant-derived molecule, yohimbine (Yoh; a beta-carboline indole alkaloid often used for ED treatment) and its potential binding phenomenon with haemoglobin (Hb). Successful binding of Yoh with Hb is evident from spectroscopic and molecular-docking results. Yoh quenched the fluorescence of Hb efficiently through a static mode. The binding affinity was in the order of 10(5) M(-1) with 1:1 stoichiometry. Thermodynamic analyses concluded that the protein-ligand association was spontaneous and was attributed to entropy-driven exothermic binding. Nonpolyelectrolytic factor was the core, dominating factor. Structural aspects were deciphered through infrared spectroscopy and computational methods. The giant 3D-protein moiety was significantly perturbed through drug binding. Hydrophobic forces and hydrogen bonding participation were stipulated by molecular modelling data. This study reveals the detailed interaction pattern and molecular mechanism of Hb-Yoh binding, correlating the structure-function relationship for the first time, and therefore holds enormous importance from the standpoint of rational and efficient drug design and development. CI - (c) 2022 John Wiley & Sons Ltd.