Sulfonamides are preventive and therapeutic agents for certain infections caused by gram-positive and gram-negative microorganisms. In this work the interactions of sulfamethazine, a representative of sulfonamide antibiotics, with two β-cyclodextrin derivatives were investigated at different pH. Results show formation of stable sulfamethazine - β-cyclodextrin complexes and reflect importance of the competition of the hydrogen bonding and electrostatic interactions. The complex geometry formed is affected by the orientation of the pH-dependent dipole moment of sulfamethazine molecule and prolonged prior the sulfamethazine molecule enters into the β-cyclodextrin's cavity. Functionalization of the β-cyclodextrin molecule doesn't affect considerably the complex stabilities, therefore the native β-cyclodextrin molecule looks the simplest and most effective inclusion host to design selective and sensitive tool for sulfamethazine sensing.