Objective: Melissa officinalis (lemon balm) and Valeriana officinalis (valerian) have been used both traditionally and contemporaneously as mild sedatives, anxiolytics and hypnotics. Recent research has suggested that both may attenuate laboratory induced stress. As the two herbs are most often sold in combination with each other the current study assessed the anxiolytic properties of such a combination during laboratory-induced stress. Methods: In this double-blind, placebo-controlled, randomized, balanced cross-over experiment, 24 healthy volunteers received three separate single doses (600 mg, 1200 mg, 1800 mg) of a standardized product containing M. officinalis and V. officinalis extracts, plus a placebo, on separate days separated by a 7 day wash out period. Modulation of mood and anxiety were assessed during pre-dose and 1 h, 3 h and 6 h post-dose completions of a 20 min version of the Defined Intensity Stressor Simulation (DISS) battery. Cognitive performance on the four concurrent tasks of the battery was also assessed. Results: The results showed that the 600 mg dose of the combination ameliorated the negative effects of the DISS on ratings of anxiety. However, the highest dose (1800 mg) showed an increase in anxiety that was less marked but which reached significance during one testing session. In addition, all three doses led to decrements in performance on the Stroop task module within the battery, and the two lower doses led to decrements on the overall score generated on the DISS battery. Conclusions: These results suggest that a combination of Melissa officinalis and Valeriana officinalis possesses anxiolytic properties that deserve further investigation.