An integrated molecular and biochemical approach was carried out to compare Moroccan and Spanish argan [Argania spinosa (L.) Skeels] ecotypes. Genetic diversity of seedlings was evaluated using Simple Sequence Repeat (SSR) markers. In addition, water stress was imposed by holding water and enzymatic peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) activities and total proteins in well-watered and water-deficient conditions were evaluated. The molecular characterization of the two ecotypes showed that the number of presumed alleles revealed by the SSR analysis ranged from 1 to 32 alleles per locus, with a mean value of 13 alleles and a mean heterozygosity value of 0.44. The assayed SSRs showed that most individuals were clustered according to their ecotype with a similar diversity level between Moroccan and Spanish ecotypes. Enzymatic activities in response to drought stress showed increase in POX and SOD activities for both ecotypes together with total protein content, but showed no significant differences in CAT activity. A potential tolerance to drought stress with increased levels of SOD activity in Spanish ecotypes grown in inland area of Alicante compared with Moroccan ecotypes grown in Essaouira, which is a coastal area, was also reported. In addition, the recovery period seemed to be sensed by argan plants as a new stress situation, as observed by the response of POX and CAT activities, suggesting an imbalance in the H2O2 metabolism. Our results suggestd an effect of geographic proximity and population isolation and/or breeding system on molecular phenotypes and responses to drought stress of the studied argan ecotypes. However, further investigations are needed to verify the induced differences.