Quinoa (Chenopodium Quinoa Willd) is recently introduced to Iran as a salt‐tolerant crop of high nutritional value. To investigate the physiological and biochemical responses of three Quinoa varieties (‘NSRCQE’, ‘NSRCQB’, and ‘Titicaca’) were compared at ≤ 2 as control, 10, 17 dS/m saline water in an experimental farm of Yazd Province, Iran in 2017-2018. This experiment was conducted as a split plot based on a randomized complete block design with three replications, whereas the salinity treatment was in the main plots and the varieties in the subplots. Salinity and varieties significantly affected DPPH radical scavenging activity, phenol, anthocyanin, flavonoid, and Malondialdehyde (MDA) contents, accumulation of Na+ and K+, and Na+/K+ ratio, as well as seed protein and saponin contents. Salinity was caused by increasing DPPH radical scavenging activity, phenol, anthocyanin, flavonoid, and MDA contents, and accumulation of Na+ in the leaves and seeds. ‘NSRCQB’ had the highest average of most measured traits under all salinity levels. The DPPH radical scavenging activity in leaves was significantly and positively correlated with phenol content, anthocyanin content, flavonoid content, MDA, Na+ accumulation in the leaves, and DPPH activity, protein content, and Na+ accumulation in the seeds. Results indicated that the salinity stress increased the amount of paracomaric, quercetin acid, and camphor acids in the leaves and seeds of Quinoa; also, the highest amount of these compounds was found by ‘NSRCQB’, also, ‘NSRCQE’ had the lowest average of most of these compounds. Based on these findings, we conclude that the salt tolerance of Quinoa grown on salt‐affected soils of Yazd, Iran was linked with better crop stand establishment, low Na+ accumulation in leaves as well as increased activities of enzymatic and non‐enzymatic antioxidants, also, ‘NSRCQB’ variety showed the best potential under salinity conditions.