In an attempt to determine the reactivity during the periodate oxidation of the vicinal amino sugar, chitosan was oxidized by KIO in a neutral medium. The reactivity was unexpectedly found to be low. The formation of di-aldehyde chitosan (DACT) might cause the low reactivity of chitosan oxidation. Therefore, density functional theory (DFT) calculations were carried out, which revealed that the greater stability of the cyclic amino iodate intermediate might retard the ring opening to form DACT. Furthermore, the affinity of the formation of two novel Schiff bases from the interaction of delivered DACT with two sulfa drugs [sulfanilamide and sulfathiazole] was also investigated using aldehyde content estimation. DACT and Schiff's bases were characterized by FT-IR spectroscopy, X-ray diffraction, and DTA analysis. The X-ray diffraction plane (110) of DACT at the high angle side was expanded more by sulfathiazole than sulfanilamide, indicating that sulfathiazole reacted effectively with DACT. The lowest interaction of DACT with sulfa drugs could be ascribed to the lowest aldehyde content and the intramolecular hemiacetal formation that hinders the Schiff's base condensation.