Mercury and arsenic are two highly toxic pollutants, and many researchers have explored the effects of the two substances on the environment. However, the research content of toxic substances in frozen periods is relatively small. To explore the spatial and vertical distribution of mercury and arsenic in the ice, water, and sediments of Wuliangsuhai Lake under ice conditions, and to assess the harm degree of the two toxic substances to human beings. We collected the ice, water, and sediments of the lake in December 2020, and tested the contents of Hg and As. The single-factor pollution index method, the local cumulative index method, and the ecological risk coding method were used to assess the pollution status in these three environmental media, and the Monte Carlo simulation combined with the quantitative model recommended by USEPA was used to assess the population health risk. The results showed that (1) The average single-factor pollution values of Hg and As in water were 0.367 and 0.114, both pollutants were at clean levels during the frozen period. (2) The mean Igeo values of Hg and As were 0.657 and −0.948. The bioavailability of Hg in the sediments of Wuliangsuhai Lake during the frozen period was high, and its average value was 7.8%, which belonged to the low-risk grade. The bioavailability of As ranged from 0.2% to 3.7%, with an average value of 1.3%. (3) Monte Carlo simulation results indicate acceptable levels of health risks in both water and ice. This study preliminarily investigated the distribution characteristics of toxic substances and their potential effects on human health in lakes in cold and arid regions during the frozen period. It not only clarified the pollution characteristics of lakes in cold and arid regions during the frozen period, but also provided beneficial supplements for the ecological protection of lake basins. This study lays a foundation for further environmental science research in the region in the future.