Abstract Onychomycosis, predominantly induced by Trichophyton rubrum , is a pervasive nail disorder within dermatology known for its high relapse rates and suboptimal patient adherence to treatment regimens. While photomedicine has emerged as a promising therapeutic modality, efficiency reductions are common due to deck obstruction in conventional light therapy. The spectral flexibility of LEDs offers a compelling solution, allowing for deeper deck penetration while maintaining efficacy. We have developed an advanced LED system with optimized optical parameters and have elucidated the antimicrobial mechanisms underlying this technology. Our research shows that an optimal wavelength of 405 nm, an energy density of 396 J/cm 2 , and an average light intensity of 140 mW/cm 2 demonstrate superior efficacy in treating onychomycosis. The antifungal mechanism of our pulsed LED system involves the induction of reactive oxygen species (ROS) within fungal mycelia, ultimately resulting in membrane damage. These insights highlight the potential of LED lighting systems as a novel antimicrobial strategy, offering a promising avenue for the treatment of onychomycosis.