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 similar to 20% in the hyper-Rayleigh 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.