Scutellaria lateriflora, a traditional herbal remedy for stress and anxiety, was tested on human volunteers for its effects on mood. In a placebo-controlled, double-blind, crossover study, 43 healthy participants were randomised to a sequence of three times daily S. lateriflora (350 mg) or placebo, each over two weeks. In this relatively non-anxious population (81% were mildly anxious or less, i.e. Beck Anxiety Inventory (BAI) scores ≤ 15), there was no significant difference between skullcap and placebo with BAI (p = 0.191). However, there was a significant group effect (p = 0.049), suggesting a carryover effect of skullcap. For Total Mood Disturbance measured by the Profile of Mood States, there was a highly significant (p = <0.001) decrease from pre-test scores with skullcap but not placebo (p = 0.072). The limitations of carryover effect, generally low anxiety scores and differences in anxiety levels between groups at baseline (p = 0.022), may have reduced the chances of statistical significance in this study. However, as S. lateriflora significantly enhanced global mood without a reduction in energy or cognition, further study assessing its putative anxiolytic effects in notably anxious subjects with co-morbid depression is warranted.