Two precise, accurate, selective and sensitive spectrophotometric methods were introduced for simultaneous determination of Cefixime trihydrate [CFX] and dexamethasone sodium phosphate [DXP] in their pure forms and pharmaceutical dosages. The first method, ratio difference method (RD), depends on the difference in amplitudes of the ratio spectra at ∆p 290-360 nm and ∆p 250-265 nm for determination of CFX and DXP, respectively. The second method, first derivative spectrophotometric method (1D), depends on measuring the peak amplitude of the first derivative selectiely at 311 and 255.6 nm for determination of CFX and DXP, respectively. The proposed methods were validated according to ICH guidelines. Satisfactory results were obtained for for determination of both drugs in laboratory prepared mixture and pharmaceutical dosage forms. The developed methods were compared with official ones.