Plant-based milk is rich in polyunsaturated fatty acids, polyphenols and other bioactive compounds. This study investigated the effect of 3 plant-based milk (flaxseed milk, oat milk and soy milk) on the ceftriaxone-induced intestinal disorders, and compared the regulation patterns associated with gut microbiome and metabolome. The results showed plant-based milk alleviated the ceftriaxone caused cecum swelling, colonic tissue damage and intestinal microecological disorders. Meanwhile, administered plant-based milk decreased levels of pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and oxidative stresses (malondialdehyde (MDA) and myeloperoxidase (MPO) in the colon, as well as increasing the levels of tight junction proteins (Occludin, Claudin-1, and ZO-1) in the colon. Moreover, administration of plant-based milk modulated the intestinal microbiota by promoting the relative levels of beneficial bacteria (Bifidobacterium), and inhibiting the harmful bacteria genus (Enterococcus). Furthermore, plant-based milk treatment significantly modulated glycerophospholipids metabolism (e.g. glycerophosphocholine) and arachidonic acid metabolism (e.g. prostaglandin G2 and arachidonic acid) in the serum. In conclusion, plant-based milk could alleviate antibiotic-related imbalance of barrier function damage, gut microbiota disorders and the reduction of metabolic disorders, which lays a foundation for exploring anti-inflammatory and intestinal micro-ecological approach to plant-based milk.