Natural products lack their charm due to several factors like absorption, first-pass metabolism, rapid biotransformation, efflux transport mechanisms, food effects, or numerous other factors which leads to low therapeutic efficacy and frequently impose a question mark over their acceptance. To resolve this issue, using the formulation optimizer Design Expert® software v.12.0, the optimal ratio of hesperidin (flavonoid)-soya Phosphatidylcholine (SPC) was calculated using factorial arithmetic, with three critical factors (complexation rate, entrapment efficacy, and drug release) considered. From the above statistical treatment, hesperidin-SPC in the optimized ratio of 1:1 was developed through conventional method. The developed product was comprehensively characterized through spectroscopic techniques (through Ultraviolet-Visible, Fourier-transformed Infrared, and Nuclear Magnetic Resonance; thermal studies (through Differential Scanning Calorimetry and Thermal Gravimetric Analysis), Crystallinity (through X-ray diffraction), morphology (through Compound Microscopy, Scanning Electron Microscopy and Atomic Force Microscopy), and Composition (Energy-dispersive X-ray spectroscopy). In addition to it, the complex was broadly studied through in-silico parameters in terms of chemistry, physicochemical, pharmacokinetics, metabolism, toxicity, and biology using the computational tool Swiss ADME. In conclusion, the critical elements were researched in silico, the best optimal ratio was established, the essential components were explored, and the negative effects of different factors were mitigated, allowing for the development of the phytosomes.