Pharmaceutical compatibility studies are considered as the most important and first phase by pharmaceutical researchers during development of pharmaceutical drug product. Attenuated total reflectance/fourier transform infrared (ATR-FTIR) is one of the few techniques currently available to pharmaceutical scientists for exploring compatibilities between active drug and inactive pharmaceutical ingredients. The present study was designed to assess the interaction among different niosomes forming components i.e nonionic amphiphiles and chondroprotective/antiinflamatory drug Diacerein by ATR-FTIR method. Physical mixtures and niosomes were prepared by physical mixing and thin film hydration method respectively. The individual niosomal components, physical mixtures as well as niosomal formulations were analyzed by ATR-FTIR technique. The spectra of Diacerein showed characteristic peaks at 3300 cm-1 (–COOH) and 760 cm-1 (m-substituted benzene), Span 60 at 2916 cm-1 (–OH), Span 80 at 1740 cm-1 (5- membered ring), Span 85 at 1643 cm-1 (ketone with 5-membered ring), Tween 20 at 1734 cm-1 (5-membered ring) and Tween 80 at 3488 cm-1 (–OH). These characteristic peaks of Diacerein were present in niosomal formulations with slight shift at 3355-3379 cm-1 (–COOH) and 760-770 cm-1 (m-substituted benzene). These results concluded that there was no significant interaction in characteristic peaks of Diacerein after combination with nonionic surfactants as physical mixture and niosomal formulations which suggested potential for niosomes to encapsulate diacerein in their microvicinity.