Entecavir (ENT), an antiviral medication, has been identified using two simple, sensitive, accurate, and precise spectrophotometric approaches that have been developed and verified. In order to produce a yellow-coloured Schiff's base product that can be detected at a maximum wavelength of 402 nm, ENT reacts with p-dimethylaminobenzaldehyde (p-DMAB) in an acidic solution. This reaction is the basis for method A. Under ideal conditions, the concentration range of 20-400 μg mL-1 agrees with Beer's law due to its excellent correlation coefficient (r2 = 0.9988) and low relative standard deviation (RSD% = 1.80). The method B approach uses cetyltrimethylammonium bromide (CTAB) and Triton X-114 as surfactants at a maximum wavelength of 415 nm to measure the amount of the yellow colour product using a cloud point extraction (CPE) methodology. Beer's law was seen to be obeyed in the concentration range of 0.1-3.0 μg mL-1, with a r2 value of 0.9995 and an RSD% of 1.50. The ideal reaction conditions include the molar ratio, solvent type, reagent concentration, and reaction time. The detection and quantification limits were calculated. With the regularly used excipients and additives, no interaction was noticed. The suggested techniques for measuring ENT in its pharmaceutical formulations were successfully applied, and the findings for pure ENT and commercial tablets were in good agreement with those from the reported approach.