Constipation is a common clinical manifestation of digestive system disorders and occurs worldwide. This study investigated the ability of Lactobacillus plantarum KSFY06 (LP‐KSFY06) to promote the action of geniposide in preventing montmorillonite‐induced constipation in Kunming mice, with the aim of providing a successful solution. The effects of LP‐KSFY06 and geniposide on constipation were measured, and the results showed that the protective effect of geniposide on constipation was enhanced by LP‐KSFY06 and that the combination resulted in increased weight, moisture content, and particle number of feces. The first black stool defecation time was decreased from 182?min to 87?min, which clearly indicates that defecating difficulty was alleviated in constipated mice. The synergic intervention of LP‐KSFY06 and geniposide (LP?+?G) assisted in maintaining the body weight of constipated mice. The LP?+?G intervention significantly increased serum levels of motilin (MTL, 167.8?pg/ml), acetylcholinesterase (AChE, 45.3?pg/ml), substance P (SP, 61.0?pg/ml), vasoactive intestinal peptide (VIP, 70.5?pg/ml), endothelin‐1 (ET‐1, 16.1?pg/ml), and gastrin (73.0?pg/ml) and remarkably decreased somatostatin (SS, 35.2?pg/ml) when compared to those indexes in the LP‐KSFY06 group and geniposide group. The LP?+?G treatment also significantly increased the mRNA expression of cluster of differentiation 117 (c‐Kit), stem cell factor (SCF), glial cell‐derived neurotrophic factor (GDNF), and remarkably downregulated the expression of inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid‐1 (TRPV1), and cyclooxygenase‐2 (COX‐2). The experimental results showed that the combination treatment has the strongest prevention effect against constipation, and LP‐KSFY06 promotes the ability of geniposide to prevent constipation. Therefore, LP‐KSFY06 is a potential probiotic strain with the capacity to prevent montmorillonite‐induced constipation.
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