Camellia seed oil (CSO), a potential prebiotic agent, can significantly increase the relative abundance of Akkermansia muciniphila (A. muciniphila) in mice gut microbiota following oral administration, this study aims to investigate the enhancing effect in vitro. The results showed that after 24‐h co‐cultivation with 0.5% (v/v) CSO, the growth of A. muciniphila increased from 11.61 ± 0.04 Log10CFU/mL to 12.17 ± 0.10 Log10CFU/mL (p < 0.05), accompanied by a reduction in the oxidation–reduction potential (ORP) value of the media from −126.67 ± 1.78 mV to −117.33 ± 0.72 mV (p < 0.05). Additionally, squalene and (+)‐α‐tocopherol, bioactive compounds present in CSO, were found to promote A. muciniphila proliferation (squalene OD600: 1.086 ± 0.002, tocopherol OD600: 1.100 ± 0.003, DMSO control OD600: 0.991 ± 0.003, p < 0.0001). Transcriptomic and metabolomic profiling revealed 464, 121, and 194 differentially expressed genes (DEGs) and 212, 160, and 156 differentially expressed metabolites (DEMs) in A. muciniphila co‐cultivated with CSO after 4, 16, and 24 h, respectively (p < 0.05). The upregulated DEGs and DEMs were primarily enriched in pathways associated with energy generation (e.g., gap, icd, sucC, GOZ73_RS04175, succinate, phosphoenolpyruvate), nucleotide metabolism (e.g., mazG, deoxyguanosine), amino acid metabolism (e.g., argF, metK, L‐tyrosine), translation (e.g., rplO, rpmC), and environmental adaptation (e.g., murA, katE, reduced nicotinamide adenine dinucleotide). These findings suggest that various bioactive compounds present in CSO exhibit prebiotic effects on the in vitro proliferation of A. muciniphila by facilitating nutrient utilization and environmental adaptation. This study provides insights into the extended utilization of CSO.