Patulin (PAT) is a common mycotoxin. Oral ingestion of PAT could damage the intestinal mucosa. Both selenium and probiotics can alleviate intestinal damage, but there are few reports on selenium-enriched probiotics. Here, we studied the protective effects of a new selenium-enriched MRS-7 (SeP) on PAT-induced jejunum injuries in mice. Results show that PAT induced jejunum injuries such as loss of crypts, ulceration of the mucosa, and intestinal epithelial barrier function impairment. However, SeP could protect against PAT-induced jejunum injuries and significantly inhibit the reduction of goblet cell numbers. SeP could not only alleviate PAT-induced oxidative stress by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the jejunum tissues but also alleviate the inflammatory response caused by PAT by reducing the levels of inflammatory factors (interleukin (IL)-6 snd IL-1β and tumor necrosis factor-α (TNF-α)) in the serum and jejunum tissues. In addition, SeP also inhibited the expression of nuclear factor-κB (NF-κB) and Toll-like receptor 4 (TLR-4), increased the expression of tight junction proteins (occludin, ZO-1, and claudin-1), and increased the selenium content in the jejunum, thereby antagonizing the jejunum injuries caused by PAT exposure. Finally, SeP rebalanced the intestinal microbiota and improved probiotic abundance such as , , , and in PAT-treated mice. These results support the possibility of SeP as a novel protective agent to mitigate the toxicity of PAT.