Quinoa proteins (QP) have promise as a potential source of novel food ingredients, and it is of great interest to know how high-intensity ultrasound (HIUS) treatments affect the properties of QP. This work aimed to study the impact of on-off time-pulses of HIUS treatments on the structural and physicochemical properties of QP; samples were treated at 5, 10, 20, and 30 min with on-off pulses of 10 s/10 s, 5 s/1 s, and 1 s/5 s). Structural changes were evaluated using PAGE-SDS, circular dichroism, fluorescence spectroscopy, and differential scanning calorimetry. Meanwhile, physicochemical properties were also examined, including solubility, Z-average, polydispersity index PDI, and Z-potential. PAGE-SDS showed the appearance of polypeptides over 190 kDa in HIUS samples-treated. All samples presented 15.6% α-helices, 31.3% β-sheets, 21.8% β-rotations, and 31.4% random coils independent of the HIUS treatment. β-Turn structures and "random coils" were not affected by HIUS. When US 10 s/10 s and 1 s/5 s were applied, an increase in the % α-helix and a decrease in β-fold were observed, which could indicate a small conversion of β-folds to α-helices. Fluorescence spectra for all HIUS showed a significant increase (23%) of average fluorescence intensity and a decrease of λmax in relation to that of the control (346 dnm and 340 nm average HIUS treatment). DSC showed one endotherm in all cases (81.6-99.8 °C), and an increase in Td was observed due to the effect of the HIUS treatment. HIUS caused a 48% increase in solubility. The Z-average of the HIUS samples compared to that of the controls showed an increase from 37.8 to 47.3 nm. PDI and Z-potential values from the QP controls and the HIUS samples did not show significance differences and presented average values of 0.466 ± 0.021 (PDI) and -16.63 ± 0.89 (Z-potential). It is possible to conclude that HIUS treatments affect the secondary and tertiary structure of quinoa proteins, and these changes resulted in an increase of solubility and particle size. HIUS treatment as a new and promising technology that can improve the QP solubility properties and in that way allow its use as an ingredient with a good source of protein to develop different types of beverages/protein sauces.