One of the leading causes of illness and mortality worldwide is cardiovascular disease. The optimum therapy in the majority of cases is accomplished by combining a number of medications, each of which has a unique mechanism of action, to treat cardiovascular disease. Entresto® tablet combines Sacubitril (SAC) and Valsartan (VAL), It is proposed to lessen the risk of cardiovascular hospitalization and heart failure-related death in those with chronic heart failure and a lower ejection fraction. The aim that initiated the work was to develop Eco- friendly sustainable spectrophotometric methods that can be employed as an environmentally friendly alternative to the methods previously reported for SAC/VAL combinations. The suggested spectrophotometric methods are constant value (CV), concentration value (CNV), Absorption subtraction (AS), and Amplitude modulation (AM). Six evaluation tools were used to evaluate the greenness and whiteness of the developed methods in order to ensure their qualitative and quantitative safety to both humans and the environment; namely, National Environmental Methods Index, the analytical eco-scale, Green Analytical Procedure Index, complementary green analytical procedure index and the Analytical GREEnness metric, and by Whiteness tool for assessing analytical chemistry method. The suggested spectrophotometric methods were successfully applied to the studied mixture. Because the zero-order spectra were directly computed without the need for any separation stages, the established concentration value approach could identify both medications without the usage of regression equations. Additionally, depending on the iso-absorptive point, both analytes could be determined via the Absorbance Subtraction and Amplitude Modulation procedures using their same regression equation.