By combining classical samplings with quantum chemistry semiempirical time-dependent Hartree-Fock calculations, the high impact of dynamic fluctuations on the NLO properties of helical strands has been evidenced. In particular, these fluctuations are responsible for relative variations of ∼20% in the hyperRayleigh responses in both pyridine - pyrimidine (py - pym) and hydrazone - pyrimidine (hy - pym) strands. Then, dynamical disorder has an even more important impact on the electric-field-induced second harmonic generation responses, whose variations can reach 2 (py - pym) or 5 (hy - pym) times their mean value. This work also highlights the relationships between the unit cell nature and helical conformation of foldamers and their second-order NLO responses. In particular, the octupolar symmetry of the hyper-Rayleigh depolarization ratios is related to the helix periodicity of three unit cells per turn in both compounds.