Global climate changes have intensified water stress in arid and semi-arid regions, reducing plant growth and yield. In this scenario, the present study aimed to evaluate the mitigating action of salicylic acid and methionine in cowpea cultivars under water restriction conditions. An experiment was conducted in a completely randomized design with treatments set up in a 2 × 5 factorial arrangement corresponding to two cowpea cultivars (BRS Novaera and BRS Pajeú) and five treatments of water replenishment, salicylic acid, and methionine. After eight days, water stress decreased the Ψw, leaf area, and fresh mass and increased the total soluble sugars and catalase activity in the two cultivars. After sixteen days, water stress increased the activity of the superoxide dismutase and ascorbate peroxidase enzymes and decreased the total soluble sugars content and catalase activity of BRS Pajeú plants. This stress response was intensified in the BRS Pajeú plants sprayed with salicylic acid and the BRS Novaera plants with salicylic acid or methionine. BRS Pajeú is more tolerant to water stress than BRS Novaera; therefore, the regulations induced by the isolated application of salicylic acid and methionine were more intense in BRS Novaera, stimulating the tolerance mechanism of this cultivar to water stress.