This paper presents a comparative study on the complexation of two xenobiotics with natural cyclodextrins. Berberine (a hepatoprotective and antibacterial agent with rigid structure) and piroxicam (an anti-inflammatory compound with more flexible structure, but similar with berberine) were encapsulated in α- and β-cyclodextrin with yields of 83-89% and 71-72%, respectively. The obtained complexes (by using the ethanol-water solution method) were characterized by scanning electron microscopy (the crystal dimensions were in the range of 800 nm to 10 µm), thermogravimetry and differential scanning calorimetry, both analyses revealed the formation of bioactive compound-cyclodextrin complexes.