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The emergence of the COVID-19 pandemic has exerted selective pressure on local medical systems, encouraging human groups to seek alternative treatments, including traditional medicine. Natural treatments are critical alternatives for Amazonian populations due to the barriers they face to access health care services. Thus, this research aimed to carry out an ethnobiological study with evolutionary and ethnopharmacological approach on the selection processes and routes of knowledge transmission about treatments for COVID-19 to understand how local medical systems in the municipality de Salvaterra are adapting to the presence of COVID-19. Data collection was carried out through semi-structured interviews applied to residents of Salvaterra who tested positive for COVID-19. The interviews were conducted between July and October 2021. Sixty-two people, 31 living in urban and 31 in rural areas, were interviewed. Most respondents (74%) used natural treatments to treat the symptoms of COVID-19. Thirty-four plant species belonging to 21 botanical families were cited. Lemon [Citrus × limon (L.) Osbeck], garlic (Allium sativum L.), and jambu [Acmella oleracea (L.) R.K. Jansen] were the most cited. The preference for using leaves and plants from managed environments in preparing herbal remedies reinforces theories that the environment can influence how people use natural resources in each biome. The prevalence of horizontal (37%) instead of vertical (30%) transmission of knowledge reinforces that more diffuse ways, such as the horizontal and diagonal, are favored in unstable environments such as those created when a new disease emerges. According to the data, age and familiarity were the most substantial biases influencing the learning of biocultural traits in the studied local medical system.