Neonatal calves exhibit heightened susceptibility to infections caused by various gut microbiota, primarily due to their immature gastrointestinal barrier functions and underdeveloped immune systems during the pre-weaning period. Calf diarrhea poses a significant risk to the health of juvenile ruminants and can result in substantial financial losses within the livestock sector. Therefore, diarrhea is a significant disease that requires improved management practices and preventive measures in cattle rearing. Antibiotics are commonly administered to combat diarrhea and promote calf growth. However, their misuse has led to increased bacterial resistance and higher levels of antibiotic residues in meat. Consequently, finding advanced and alternative ways to treat newborn calf diarrhea for enhanced livestock production and public health is a significant challenge. Probiotic administration can offer significant advantages such as improving the internal microenvironment of the gut and enhancing the host’s immune response, thereby reducing the likelihood of gastrointestinal diseases. Additionally, probiotic supplements have been formulated as alternatives to antibiotic treatment to upgrade animal health and productivity, and are essential for maintaining the balance of the gut microbiota. The treatment of calves with probiotic supplementation has emerged as a significant area of research. This review highlights the research progress on the pathogenesis of neonatal calf diarrhea and the mechanism of action of probiotics to provide new insights into the prevention and treatment of diarrhea in calves.