Tungiasis (sand flea disease) is a neglected tropical disease, prevalent in resource-poor communities in South America and sub-Saharan Africa. It is caused by an inflammatory response against penetrated female sand fleas (Tunga penetrans) embedded in the skin of the host. Although associated with debilitating acute and chronic morbidity, there is no proven effective drug treatment. By consequence patients attempt to remove embedded sand fleas with non-sterile sharp instruments, such as safety pins, a procedure that represents a health threat by itself. In this proof-of-principle study we compared the topical application of a mixture of two dimeticones of low viscosity (NYDA) to the topical application of a 0.05% solution of KMnO4 in 47 school children in an endemic area in rural Kenya. The efficacy of the treatment was assessed during a follow up period of seven days using viability signs of the embedded parasites, alterations in the natural development of lesion morphology and the degree of local inflammation as outcome measures. Seven days after treatment, in the dimeticone group 78% (95% CI 67–86%) of the parasites had lost all signs of viability as compared to 39% (95% CI 28–52%) in the KMnO4 group (p<0.001). In the dimeticone group 90% (95% CI 80–95%) of the penetrated sand fleas showed an abnormal development already after 5 days, compared to 53% (95% CI 40–66%; p<0.001) in the KMnO4 group. Seven days after treatment, signs of local skin inflammation had significantly decreased in the dimeticone group (p<0.001). This study identified the topical application of dimeticones of low viscosity (NYDA) as an effective means to kill embedded sand fleas. In view of the efficacy and safety of the topical treatment with dimeticone, the mechanical extraction of embedded sand fleas using hazardous instruments is no longer warranted.