The aim of this study was to examine the effectiveness of Enzyme-Treated Asparagus Extract (ETAS) on improving stress response. A randomized, double-blind, placebo-controlled cross-over trial was undertaken in healthy volunteers. ETAS (150 mg/d) or a placebo was consumed for 28 d, with a washout period. Psychological parameters were examined using a self-report scale questionnaire and psychological stress was applied using the Uchida-Kraepelin (U-K) test. During the stress load, autonomic nervous function was analyzed. After the stress load, a profile of mood states (POMS) psychological rating was performed, and serum cortisol, plasma catecholamine, salivary secretory immunoglobulin A (sIgA), and salivary cortisol were analyzed. ETAS intake improved the self-reported rating for the items “Feel tired,” “Hard to get up,” and “Feel heavy” in the psychological questionnaire; ameliorated the self-reported rating for the items “Depression-Dejection” and “Fatigue” in the POMS questionnaire; and increased salivary sIgA levels after the U-K test. In contrast, serum and salivary cortisol levels, and plasma catecholamine did not change. During the U-K test, ETAS significantly upregulated the sympathetic nerve activity. Furthermore, ETAS intake significantly increased the number of answers and the number of correct answers in the U-K test, suggesting that it might improve office work performance with swiftness and accuracy under stressful conditions. In conclusion, ETAS supplementation reduced feelings of dysphoria and fatigue, ameliorated quality of sleep, and enhanced stress-load performance as well as promoted stress response by increasing salivary sIgA levels. These data suggest ETAS intake may exert beneficial effects, resulting from well-controlled stress management, in healthy individuals.