The role of the wet market (traditional markets) in Asia is crucially important and is considered the main channel for buying and selling goods. As one of the developing countries, the Mekong River Delta (MRD) region in Vietnam also has a deep tradition from many generations through wet markets. However, the Covid-19 pandemic has caused significant impacts on this distribution channel when most of the wet markets were restricted from operating and required to tighten protective measures. From March 2020 until now, the Vietnam Ministry of Health has always encouraged people, especially in crowded places such as wet markets, to follow the 5K rule (this rule issued by the Vietnam government includes 5 measures to protect people). However, understanding people's behavior and awareness about these safety measures are important to help policymakers establish the necessary and reasonable solutions to protect people and this traditional distribution channel. This research, therefore, aims to search for solutions to improve the effectiveness of hygiene and safety practices at wet markets in MRD Vietnam. Primary data from the direct interview of 400 local people and group discussions with experts who are market management boards and local officials are used for analysis. The research results reveal that the majority of local traders and market-goers have an awareness of the current pandemic as well as good compliance with hygiene and safety practices in general and disease prevention in particular. In addition, the Logit model results indicated that the determinants of local people's behavior to adopt safety measures including gender and protection and prevention activities by wet market management board such as asking people to wear the mask, careful guidance and allow take-away only in the wet market.