Abstract: Oflox-TZ, Dto, and Ofnida syrup are well-known antimicrobial combination medications used to treat illnesses caused by parasites and bacteria.Environmentally sustainable model creation for antimicrobial compounds utilizing chemometric application, isosbestic point, and dual wavelength assisted by spectrophotometric and chromatog. anal. using ANOVA comparison with all developed methods.Deconvolution of the spectral overlaps and harmful use of organic solvents in spectrophotometric and chromatog. conditions with these combinations were performed using the partial least squares method, either with or without variable selection methods such as principal component regression.A good agreement was found when comparing the findings of the developed methods statistically to an ANOVA, indicating the efficacy of the suggested methodol.Calibration and validation sets comprising 24 and 12 samples, resp., were carefully developed using partially factorial designs for the experiments at different dosages.The developed models were validated according to established International Council for Harmonisation (ICH) strategies.For the dual-wavelength approach, Beer′s plot confirmed linearity between 2 and 12 μg/mL for (OFL) and 5 and 30 μg/mL for Tinidazole (TZ) resp.The mean percent recoveries were found to 101.0% and 102.0% for OFL and TZ.Chemometrics-assisted UV spectrophotometry, employing both partial least squares (PLS) and principal component regression (PCR) anal. models, yielded mean OFL recoveries of 102.3% (PLS) and 102.4% (PCR), and TZ recoveries of 102.6% (PLS) and 102.6% (PCR).Addnl., chromatog. model development using hydrotropic solutions yielded mean percentage recoveries of 100.2% and 100.6% for OFL and TZ, resp., in com. drug formulations.The study found that the proposed chemometric-assisted spectrophotometric and chromatog. methods could reliably determine OFL and TZ concentrations in both laboratory-prepared mixtures and pharmaceutical preparations, thereby proving them to be useful anal. instruments for quality control and in-process testing of different pharmaceutical drug preparationsThis approach provides a significant outcome over the use of less polluted solvents, making it more precise and economical.Graphical Abstract: