Objectives: This study aimed to develop and validate two simple, accurate, selective, reproducible and sensitive spectrophotometric methods for the determination of diloxanide furoate in the presence of its alkali-induced degradation product without preliminary separation. Methods: (A) ratio difference spectrophotometry method, where the peak amplitudes of ratio spectra were measured at 270 nm and 240 nm, (B) mean centering method, where the peak amplitudes were measured at 270 nm. All methods were applied in the range of (2- 30 μg mL-1). Results: These methods were validated according to International Conference on Harmonization (ICH) guidelines and successfully applied for determination of diloxanide furoate in Furamebe® tablets. The obtained results were statistically compared with those of the reported method by applying t-test and F-test at 95% confidence level and no significant difference was observed regarding accuracy and precision. Conclusion: The proposed methods are simple, rapid, economic, accurate and precise to determine diloxanide furoate in the presence of its alkali-induced degradation product without previous separation steps.