Spectrophotometric methods were introduced for the simultaneous determination of Amoxicillin (AMX) and flucloxacillin(FLX) in their pure forms and  capsules pharmaceutical formulations. The first method was ratio difference (RD), in which the amplitude difference between 238 and 255 nm for AMX and between 254 and 238 nm for FLX were measured.The second one was mean centering of ratio spectra (MCR) in which the peak amplitude at 286nm for the determination of AMX and the peak amplitude at 236 nm for the estimation of FLX were measured. The third method was Area under the curve (AUC) where the range of 226 and 236 nm were adopted for AMX determination and of 240 and 247 nm for FLX determination. All of the previous methods were successfully used for quantitation of AMX and FLX in concentration ranges of 5-50µg/ml and 10-70µg/ml, respectively by RD and MCR methods and of 10-60µg/ml and 10-70µg/ml, respectively for AMX and FLX by AUC method. All of the developed methods were validated using ICH guidelines and statistically compared to a reported method. The adopted methods can be applied for the regular analysis of AMX and FLX mixture in QC laboratories.