Isoniazid, the first line anti-tuberculosis agent, and its complexes with β-cyclodextrin were investigated. The 1:1 stoichiometry ratio for the complex has been proposed based on Job’s plot and AL diagram from phase solubility studies. These results were further interpreted using PM3 semi-empirical method molecular modeling. The most optimum position of isoniazid was located at the center of β-cyclodextrin cavity with pyridine ring of isoniazid facing towards primary rim of β-cyclodextrin with minimum energy of -2.2990407 Hartree (-1442.67 kcal mol-1). Two intermolecular hydrogen bonds were formed and weak molecular interaction between β-cyclodextrin and isoniazid was detected. In conclusion, the theoretical results were in good agreement with experimental results.