Cefixime Trihydrate and Moxifloxacin Hydrochloride combination was given approval by Central Drug Standard Control Organization (CDSCO) on 8th August 2011. There are very few methods have been reported for simultaneous estimation of Cefixime Trihydrate and Moxifloxacin Hydrochloride. Spectrophotometric methods (Q-Absorption Method and First Derivative Method) and RP- HPLC method were developed and validated for simultaneous estimation of Cefixime Trihydrate and Moxifloxacin Hydrochloride in combined dosage form. Analysis was carried using two methods - spectrophotometric method and RP-HPLC method. The developed methods were simple, rapid, precise,and accurate and so it can be successfully used for the simultaneous estimation in quality control laboratory.