Recently, Countless people have become affected as a result of the Covid-19 crisis. Even after recovery, COVID-19 can lead to respiratory difficulties and lung impairment consequently; bacterial infections have a good possibility of infiltrating our respiratory system due to reduction in respiratory immunity. Therefore, the importance of the chosen mixture of doxycycline and ambroxol becomes clear here curing bacterial illnesses invade respiratory tract. The ternary blend of (DOX) doxycycline hyclate, (AMB) ambroxol hydrochloride, (IMP) chemical ambroxol precursor, and pharmacopeial impurity was quantified using four contemporary, selective, and straightforward methods. Method (I) was area under the curve spectrophotometric method (AUC), where zero order absorption spectra were used for calculating the area under the curve of AMB, IMP, and DOX in ranges of 205–219, 222–245, and 264–290 nm, respectively. Each component's absorptivity values (a) at the chosen area were computed. Method (II) was differential dual wavelength (DDW), where upon collecting the first derivative spectra of AMB, IMP, and DOX, amplitudes at 252–263.4, 236–246.6, and 388.8–420 nm were subtracted, consecutively. Method (III) the mean centering of ratio spectra spectrophotometric method (MCR), peak to peak amplitudes on these resulted spectra were measured at (258.2 and 258.4 nm) for AMB, (264.4 and 264.6 nm) for IMP, and at (230.4 and 230.6 nm) for DOX. In addition, method (IV) HPTLC using a stationary phase made of silica gel HPTLC plates that had been pre-treated with 0.27 M di-sodium-EDTA (pH 9 with 21 % sodium hydroxide). The platform is developed using the eluent of ethyl acetate, acetone, distilled water, and acetic acid (9:2:0.7:0.55, by volume) and scanning by employing ultraviolet light regarding AMB and IMP at 254 nm while DOX at 380 nm. For validating the developed procedures, ICH principles were adhered to. The proposed methods were successful in studying dosage form containing investigated substances. The developed techniques' greenness features were assessed using a variety of greenness parameters, and an environmental evaluation comparison between the current methods and the reported one was done. Obtained methods' statistical analyses were also performed.