Durum wheat, Triticum turgidum subsp. durum (Desf.) Husn., is one of the most salt-sensitive cereal crops, but the physiological responses of different cultivars to salt stress vary. Cultivars that are suited to arid conditions like in Algeria may not necessarily be tolerant to increased salinity. When 10-day seedlings of Algerian durum wheat varieties Hedba 3 (HD3) and Mohamed Ben Bachir (MBB) were subjected to salt stress, they accumulated proline and expressed stress-related and proline metabolism genes in a classic salt-stress response. Expression of the selective sodium transporter genes HKT1;4-1 and -2 was found to be organ-specific and modulated by salt stress in both cultivars. Adding proline to the salt-containing growth medium alleviated some salt stress effects such as decrease in water content, ion leakage and expression oxidative stress markers while growth parameters were partially rescued to different extents in the two cultivars. Durum wheat seedlings accumulated sodium ions (Na+) at the expense of potassium ions (K+) under salt stress which lowered the in planta K+/Na+ ratio. The two durum wheat cultivars studied here respond differently to salt stress in terms of responsiveness to proline, HKT1;4 gene expression, and Na+ and K+ accumulation. Notably, salt stress can be partially alleviated by proline in the drought-resistant cultivar MBB, even though it is relatively salt sensitive.