Head louse infestations remain a global public-health concern due to increased resistance of lice to artificial pediculicides. In Thailand, there is a lack of comparative data on the current efficacy of pediculicides for treating head lice. In this study, we explored the status of botanical and toxic synthetic pediculicides with that of 4% dimeticone liquid gel for treating head lice in Thailand. Theex-vivopediculicidal activity of various pediculicidal shampoos available at drugstores in Thailand was assessed and compared with that of 4% dimeticone liquid gel. The shampoos chosen were based on active ingredients toxic to lice (1% permethrin, 0.6% carbaryl, 0.15%Stemonaroot crude extract, or mixed plant extracts), whereas dimeticone acts physically on lice. We found that exposure to 4% dimeticone liquid gel following the manufacturer’s instructions completely killed 100% of head lice in 15 min, whereas other pediculicide products failed to kill the great majority of head lice, whether treatment was for 10 min (resulting in 0% to 50.0% mortality) or 30 min (resulting in 17.0% to 60.0% mortality). We also extended a clinical assessment to confirm the efficacy of 1% permethrin for treating head lice in infested schoolchildren. In this clinical assessment, none of the 26 children treated with 1% permethrin shampoo achieved a cure after two applications. These results highlight that 4% dimeticone demonstrated a higherex-vivopediculicidal efficacy compared to both chemical and botanical pediculicides in Thailand. Conversely, 1% permethrin showed low efficacy in both laboratory and clinical assessments. Given its physical mode of action, 4% dimeticone merits consideration as an alternative treatment option for lice in Thailand, particularly in cases where treatment with toxic pediculicides has proven ineffective.