Two simple and rapid spectrophotometric methods were developed for the resolution and analysis of the binary mixture of glyburide (GB) and metformin HCl (MF) in tablets. The first method, zero-crossing first derivative spectrophotometry, depends on measuring the first derivative values at 314.7 nm for GB and 228.6 nm for MF. The second method, ratio first derivative spectrophotometry, depends on measuring the amplitudes of the first derivative of the ratio spectra at 314.7 nm for GB and 238.0 nm for MF. The calibration graphs were linear over the range of 10-125 μg/mL for GB and 2-18 μg/mL for MF. The proposed methods were applied successfully to the assay of these drugs in commercial tablets. The developed methods were able to solve the problem arising from the coformulation of GB and MF in the ratio of 2.5:500, 5:500 or 2.5:400 (w/w), respectively in addition to the increase of the specific absorbance of MF (the major component) over that of GB (the minor component). The results were statistically compared with those obtained using a reference HPLC method and were found to be in good agreement.