In this study, phytochemically characterized extracts from the fruits of Chaenomeles japonica (CJ), Cornus mas (CM), and Hippophaё rhamnoides (HR) were investigated using an interdisciplinary approach for their effects on human gut microbiome (GM) composition and selected health parameters in a preclinical model organism, Caenorhabditis elegans. Initially, due to the availability of proteomics data of the probiotic bacterium Bacillus subtilis, analysis was conducted in silico to investigate the impact of phytochemicals from CJ, CM, and HR on its nucleases. Next, the extracts were incubated with human fecal slurry (FS) for 24 and 72 h, and the isolated genomic DNA was analyzed using next-generation sequencing (NGS) of bacterial 16S rRNA genes. These data revealed no significant alterations in GM between the different extracts. In the GM analysis, B. subtilis was not detected, which may be related to the interaction of its enzymes with the phytochemicals. Principal coordinate analysis showed that the extract type influences community composition, particularly after prolonged time. A further focus was on survival, fat accumulation, and Aβ proteotoxicity in extract-treated nematodes. All extracts were well tolerated up to the highest tested concentration (200 μg/mL). Notably, the CM extract significantly increased nematode survival by 23% at 200 μg/mL, while HR demonstrated the most pronounced effect on fat reduction, markedly decreasing lipid accumulation in genetically modified SS104 worms at the same concentration. These findings suggest that while the extracts do not substantially modulate GM composition in vitro, they exert distinct beneficial effects on metabolic and longevity-associated parameters in C. elegans.