Two simple, accurate, sensitive and reproducible methods have been developed and subsequent validated for the determination of Dothiepin Hydrochloride in presence of its oxidative and photo-degradates, as stabilityindicating studies. In the spectrophotometric method, zero-crossing technique was adopted for determination of the investigated drug in presence of its oxidative and photo-degradates, by the use of derivative and derivative ratio techniques, respectively.While, the second method was isocratic reversed-phase (RP) stability-indicating high-performance liquid chromatographic method, which was adopted for determination of Dothiepin Hydrochloride in presence of its oxidative and photo-degradates. The chromatographic separation was achieved isocratically by using a mobile phase of acetonitrile: phosphate buffer (50:50, v/v), adjusted to pH 7.0 using orthophosphoric acid and 0.5 % triethylamine. The analysis was carried out usingAgilent eclipseXDBC18 column [150mmx 4.6mm, 5 µm] at flow rate of 1.2ml.min-1 and the UVdetection at 230 nm.All the proposedmethodswere validated according to the International Conference onHarmonization (ICH) guidelines reference and successfully applied for determination ofDothiepin Hydrochloride in pure form, in laboratory preparedmixtures and in pharmaceutical preparations. The obtained results were statistically compared to the reference method of analysis for Dothiepin Hydrochloride and no significant differences were found.