Oral nutrition supplements (ONS) are widely recommended for the management of unintentional weight loss in patient populations, long-term care residents, and community-dwelling older adults. Most marketed ONS are ultra-processed, with precision nutrition and aseptic composition, as well as convenience and availability, driving their selection. However, therapeutic effectiveness is mixed and the potential health risks of consuming ultra-processed ONS long-term in lieu of less-processed foods have received little attention. A diverse and balanced microbiota supporting immunity and wellness is maintained by a diet rich in plant-sourced foods. The implications of ultra-processed ONS displacing plant-sourced foods, and specifically the potential for undesirable impacts on the gut microbiota, require consideration. Most ONS are either devoid of fiber or are supplemented with isolated or purified fibers that may contribute to adverse gastrointestinal symptoms and appetite suppression. In contrast, the diversity of microbial-available, nondigestible carbohydrates, together with the array of phytochemicals found in plant-sourced foods, support microbial diversity and its resiliency. This review outlines the clinical dilemma of recommending commercial ultra-processed ONS vs nutritionally adequate (eg, high-energy/high-protein) foods and beverages that contribute to diet quality, maintenance of a diverse and stable gut microbiota composition, and support nutrition status and health. Ultra-processed ONS may fall short of expected health benefits, and overreliance may potentially contribute to the risk for patient and older adult populations because of the displacement of a variety of healthful foods.