Two novel separation methods have been presented for the concurrent assessment of flumethasone pivalate (FP) and clioquinol (CL) in their combinations in ear drop formulations or in the presence of phenoxyethanol preservative (PEP) in their cream formulations. The first method is an innovative thin-layer chromatographic (TLC) method. The optimal separation was accomplished via silica gel aluminum plates F254, with a mixture of benzene, ethyl acetate and formic acid (5:5:0.2, in volumes) as the mobile system. In Method II, a new ultra-high-performance liquid chromatographic method (UHPLC) with a photodiode array detector (PDA) was presented. A reversed-phase inertsil ODS 5 µm C 18 packed column (100 Å, 4.6 mm internal diameter (I.D.) × 50 mm) at 30 °C was employed. Elution was completed in 3 min. Unfortunately, greener solvents were tested as a mobile phase, but an asymmetric peak for CL was noted. In addition, the new UHPLC method has a priority over the old HPLC one by Sayed et al., 2014, in terms of quickness and avoiding interference from the PEP preservative. Concerning the TLC method, the novel TLC method has the advantage of preventing the interference of PEP. This paper represents the first analytical approach for the concurrent assay of FP and CL in the presence of the preservative phenoxyethanol in the cream formulation.