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Co-fermentation with bacteria and enzymes can reduce sugar content in palm kernel cake (PKC); however, the chemical changes and their effects on cell functionality are unclear. This study investigated the active components in pre-treated PKC extracts and their effects on pig small intestine IPEC-J2 cell proliferation and LPS-induced inflammation. The extracts contained 60.75% sugar, 36.80% mannose, 1.75% polyphenols and 0.59% flavone, as determined by chemical analyses, suggesting that the extracts were palm kernel cake oligosaccharides (PKCOS). Then, we found that 1000 µg/mL PKCOS counteracted the decrease in cell viability (CCK8 kit) caused by LPS induction by 5 µg/mL LPS (<i>p</i> < 0.05). Mechanistic studies conducted by RNA-seq and qPCR analyses suggested PKCOS promoted cell proliferation through the upregulation of <i>TNF-α</i>, <i>PI3KAP1</i>, <i>MAP3K5</i> and <i>Fos</i> in the PI3K/MAPK signalling pathway; alleviated inflammation caused by LPS via the downregulation of the target genes <i>Casp3</i> and <i>TNF-α</i> in association with apoptosis; and regulated the expression of the antioxidant genes <i>SOD1</i>, <i>SOD2</i> and <i>GPX4</i> to exert positive antioxidant effects (<i>p</i> < 0.05). Furthermore, PKCOS upregulated <i>SLC5A1</i> (encoding SLGT1), <i>HK</i> and <i>MPI</i> in the glycolytic pathway (<i>p</i> < 0.05), suggesting cell survival. In summary, PKCOS has positive effects on promoting swine intestine cell proliferation against inflammation.