During the current Coronavirus Disease 19 (COVID-19) pandemic, regular handwashing and other hand hygiene practices as the primary infection prevention program are highly encouraged. Notwithstanding the noticeable benefits in combating viral infection, hand hygiene practice potentially promotes dysbiosis of the skin microbiome. This review aimed to summarize the possible impacts of hand hygiene practices using soap products and alcohol-based hand rubs (ABHR) on the homeostasis of human skin microbiota. We discuss recent findings to provide evidence of the effectiveness of hand hygiene practices in viral infection control, the role of the skin microbiome in human health and the effects of hand hygiene practice on the homeostasis of the skin microbiome. Finally, this review also suggests improving research and practice of hand hygiene in response to the ongoing COVID-19 pandemic.