Amylose or pea starch‐indomethacin systems are prepared using two different methods: The alkaline method, where the samples are prepared by mixing alkaline aqueous solutions of glucan and indomethacin at pH 12, and the sonication method, where the samples are prepared at pH 7 by mixing a glucan aqueous solution with indomethacin dispersed in water in the presence of cholate salts using sonication. The aim is to assess whether V‐amylose complexes can be formed with the drug indomethacin as the guest molecule. Experimental techniques, such as Raman Spectroscopy, X‐ray Diffraction, Differential Scanning Calorimetry, Optical Microscopy, and Confocal Laser Scanning Microscopy, verify the presence of the drug molecules in the examined systems. The results indicate that the sonication method is more effective for the complex preparation. However, even in this case, a very limited complexation is achieved. The bioavailability of the systems is evaluated using in vitro methods, simulating gastric, and intestinal conditions. It is shown that the systems matrix provided only limited protection to indomethacin molecules up to their release in the small intestine. Thus, it is concluded that indomethacin molecules are rather physically entrapped within the amylose or starch matrix than in the interior of the amylose helices.