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Leech attachment is a common nuisance to outdoor recreationists and farmers in aquatic environments. Consequences include bleeding, infection, and, rarely, death. Methods to prevent leech attachment are anecdotal and individual; effective repellent formulations with universal applicability are needed. In this study, icaridin is demonstrated to be repellent and toxic to aquatic leech, and formulation of icaridin loading nitrocellulose (Icar-Nitr) is proposed as a new leech repellent. The nitrocellulose provided sustained drug release and waterproof properties. One optimal formulation, 10-Icar-Nitr, proved effective for leech repelling in aquatic environment. Using a rat model, the same formulation also showed removal and killing after leech attachment. The nitrocellulose reduced percutaneous absorption of icaridin, and 10-Icar-Nitr showed good biocompatibility. This study provides a potential new and practicable strategy for prevention and removal against leech attachment and bites.