The treatment of gustatory sweating in diabetes mellitus is usually with oral anti-cholinergic drugs, but these frequently lead to unacceptable side effects. Glycopyrrolate is an anti-muscarinic agent that can be applied topically and is efficacious in gustatory sweating occurring in other conditions. In a double-blind placebo-controlled crossover study, we assessed the value of glycopyrrolate in 13 diabetic patients with gustatory sweating. Sweating was measured by a sweat challenge, and diaries recorded by the patients throughout the 2 weeks of each treatment period. Compared to placebo, glycopyrrolate reduced the sweat response to a challenge by 82% (p < 0.01). The frequency of episodes of gustatory sweating during the treatment period was also reduced by 51% (p < 0.01), with a nearly 100% reduction in the frequency of episodes of severe sweating (p < 0.01). In conclusion, topically applied glycopyrrolate is a very effective treatment in reducing both the severity and frequency of diabetic gustatory sweating.