This study examines the inhibitory activity of spice extracts on histidine decarboxylase which synthesizes histamine, a bioactive amine participating in gastrointestinal ulcer and allergy ailments. It was found that most of both the water and ethanol extracts affected the enzymatic activity, the majority exhibiting inhibitory activity, although the degree of inhibition varied widely. Cinnamon, allspice, and Japanese pepper were strong inhibitors among the ethanol extracts, with the water extracts of cinnamon, allspice and Japanese pepper also exhibiting strong inhibition, together with other extracts from sage, bayleaf, rosemary, etc. Ethanol and water as the solvents had an opposing effect on some of the spice extracts. For example, the water extract of peppermint was inhibitory, while the ethanol extract enhanced the enzyme activity. Individual known components of the ethanol extracts of various spices were examined for their inhibitory effect on histidine decarboxylase, most of them exhibiting inhibition, although not as strongly as the crude extracts. An additive effect of spice components may be important for this inhibition. We demonstrate that it was possible to identify suitable inhibitor(s) of histidine decarboxylase by using our evaluation method. The inhibitors found by our method may be used as anti-allergic agents without any severe side effects. Food components having anti-allergic and anti-ulcer properties are also highly desirable with future development.