<p>Obsessive-compulsive disorder (OCD) is a mental illness of unwanted recurrent thoughts and compulsive behaviors. The significance of the microbiota-gut-brain axis has been increasingly documented in the manifestation of neuropsychiatric disorders. Herein, we investigated the impact of synbiotic containing <i>Faecalibacterium prausnitzii</i> ATCC 27,766 <i>(F. prausnitzii</i>) and prebiotics [fructooligosaccharides (FOS) and galactooligosaccharides (GOS)] on quinpirole-induced OCD-like symptoms in rats. Repeated quinpirole injections led to compulsive- and anxiety-like behaviors, as rats showed reduced head-dipping behavior in the hole board test, increased marble burying and self-grooming behaviors, and decreased exploration of open areas during elevated plus maze testing. Treatment with <i>Faecalibacterium prausnitzii</i> combined with prebiotics (FOS and GOS) over a six-week period improved these behavioral alterations, reducing signs of repetitive, compulsive, and anxiety-related behaviors. Notably, neither open-field locomotion nor body weight showed significant differences between the experimental groups. In molecular studies, synbiotic treatment showed a reversal of elevated levels/mRNA expression of TNF-α and IL-6 in the frontal cortex and increased mRNA expression of tryptophan hydroxylase (TPH-1) in the colon of quinpirole-injected rats. The cohorts of rats received synbiotic treatment showed normalization of intestinal parameters, including fecal short-chain fatty acid concentrations (acetate, propionate, and butyrate), as well as improvements in intestinal morphology markers such as villi-crypt ratios, goblet cell populations, occludin and TPH1 expression in the colon. These findings highlight the potential benefits of synbiotic laden with <i>F. prausnitzii</i> and prebiotics (FOS + GOS) in alleviating quinpirole-induced OCD-like symptoms by reshaping animal gut-brain-axis mediators.</p> Graphical Abstract <p></p>