The present work describes HPTLC method for analysis of Nadifloxacin and Mometasone furoate in topical cream. The separation was carried out on Merck precoated silica gel aluminium plate 60 F254 using Dichloroethane: Diethyl ether: Ammonia: Methanol: Ethyl acetate (6: 3: 0.2: 1.75: 3.5 v/v) as mobile phase. The densitometric scanning was carried out at 254 nm. Response was found to be linear in the concentration range of 1000–3000 ng /band with correlation coefficient (r2 = 0.997) for Nadifloxacin and 100-300 ng/band with correlation coefficient (r2 = 0.995) for Mometasone furoate. The method was validated as per ICH guidelines. The method was successfully applied for the analysis of drugs in pharmaceutical formulation.