Abstract: To investigate the effects of probiotic formulation on symptoms of atopic dermatitis (AD), probiotic strains (have been reported to be associated with immune responses in dermatitis), as well as plant-derived compounds (including fructo-oligosaccharides) were selected based on preliminary experimental results and related reports. To investigate the synergistic enhancement based combinatorial treatment strategies for probiotics and plant-derived compounds, the effects of mixed probiotics, mixed plant-derived compounds, and a probiotic-phytochemical synbiotic formulation (a combination of the aforementioned mixed probiotics and mixed plant-derived compounds) on AD were assessed. The results indicated that compared with the mixed probiotic and mixed plant compound treatments, the probiotic–phytochemical synbiotic formulation contributed to a more pronounced alleviation of AD symptoms, characterized by a significantly stronger inhibition of inflammatory cell infiltration in AD-like skin lesions (P<0.001), a more substantial reduction in total levels of immunoglobulin E in serum and content of inflammatory cytokines in dorsal skin tissues, and a more significant elevation of interferon-γ. Additionally, analyses of the gut microbiota revealed that compared with the AD model group, intervention using the probiotic–phytochemical synbiotic formulation promoted increases in the relative abundances of beneficial bacterial genera, including Akkermansia, Bifidobacterium, Turicibacter, and Faecalibaculum, whereas at the OTU level, there was a significant elevation in the relative abundance of Bifidobacterium animalis (P<0.05). Furthermore, microbe–microbe network and correlation analyses revealed a significant association between the enriched gut bacterial composition following intervention with the probiotic–phytochemical synbiotic formulation and the levels of immune-inflammatory factors (P<0.05). In summary, compared with mixed probiotics and plant-derived compounds, a probiotic–phytochemical synbiotic formulation was more effective in alleviating AD, conferring measurable synergistic effects and contributing to the amelioration of AD via routes involving the modulation of both immune responses and the gut microbiota.