By molecular mechanics method and quantum chemical calculation was applied to examine the most stable conformations and flexible properties of side chains of diketopiperazine cyclic dipeptides with antibacterial, anticancer and antioxidant activity. By calculations on diketopiperazine dipeptide cyclo(D‐Tyr‐D‐Phe) and its analogs cyclo(L‐Tyr‐L‐Phe), cyclo(LTyr‐D‐Phe), cyclo(D‐Tyr‐L‐Phe) as a function of the side‐chain torsion angles were determined their energetically preferred conformations. The obtained results of conformational analysis were used to found the relative position of the side chains of residues in the stable conformations of the dipeptides. Our calculations bring out for each cyclic dipeptides formed the two types of conformations as the most favorable. One of them conformation formed asymmetric arrangement of side chains with the tyrosine ring folded over the diketopiperazine ring, but second dipeptide conformation formed with extended arrangement of side chains. Quantum chemical calculation shed light on the structural modifications between the different cyclic dipeptides.