Signal transformation (derivative and wavelet) was applied to UV spectra and ratio spectra to directly quantify spiramycin and metronidazole in binary mixtures. Linear calibration graphs were examined for either drug in the concentration range of 6.25 – 25 mg/L with R2 > 0.990. First derivative-transformed (i.e., using Savitzky-Golay filter) and wavelet-transformed (i.e., using families such as sym6, haar, db5, bior2.4, rbio2.4, meyr with scaling factor = 256) UV spectrophotometric methods were statistically comparable to the RP-HPLC reference method (p > 0.05) with regard to accuracy and precision when assaying spiramycin and metronidazole in their coated tablets. These analytical methods used only green solvent, and proved to be time-saving and cost-effective.