The present study is aimed at investigating the drought stress responses of two Egyptian rice varieties (Sakha 104 and Giza 178) after grain soaking in cobalt nutrient solution at the optimum concentration before sowing in soil and gaining physiological insights into drought tolerance in rice plants. The drought stress was applied according to different irrigation intervals (control; irrigation every 4 days, moderate; irrigation every 6 days; and severe; irrigation every 8 days). The results showed variable reductions in the tiller number/plant, tiller barring panicles/plant, panicle length/plant, panicle weight/plant, 100-grains weight, and harvest index in both varieties under drought stress. Also, drought stress significantly reduced the nutritional value of the grains such as sucrose, soluble sugars, polysaccharides, total carbohydrates, total protein, vitamins (B9 and B12), as well as element content (Ca²⁺, Na⁺, Fe²⁺). Meanwhile, there was a notable increase in the grain contents of glucose, K⁺, K⁺/Na⁺ ratio, and Co²⁺ of both rice varieties under drought conditions. Cobalt application significantly alleviated the detrimental effects of drought stress by improving the above-mentioned parameters comparably in both rice varieties, particularly in Giza 178. The results of sodium dodecyl-sulfate polyacrylamide gel electrophoresis of drought stress either alone or in combination with cobalt nutrition showed de novo synthesis of protein pattern bands in the grains with the molecular weights of 33, 91, and 110 kDa in the Sakha 104 variety and 42, 53, 57, 60, 71, 91, and 97 kDa in the Giza 178 variety.