Objectives: The gut-brain axis has emerged as a promising avenue for understanding the bidirectional communication between the gut microbiota and the central nervous system. This study investigated the potential impact of probiotics, Lactobacillus acidophilus (LA-5), Lactobacillus paracasei (L. casei 431), and Bifidobacterium lactis (BB-12), as well as their combination, on dental pulp pain management and cognitive functions. Design: Forty-eight male Wistar rats were randomly assigned to six experimental groups (n = 8). The probiotics (109 CFU) were orally administered for 14 consecutive days. Capsaicin (100 µg) was used to induce inflammatory pulp nociception. The Morris water maze task was used to evaluate learning and memory performance. Levels of the interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) cytokines in the animals' trigeminal ganglion (TG) and the brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), tropomyosin receptor kinase B (Trk-B) and Cyclooxygenase-2 (COX-2) genes in the animals' hippocampus were determined using western blotting and RT-PCR, respectively. Results: Intradental application of capsaicin induced nociceptive behavior and increased IL-1β and TNF-α in the TG of rats. Probiotics could attenuate nociception and prevent IL-1β and TNF-α overexpression. Furthermore, pain induced cognitive impairments, decreased BDNF, NPY, and Trk-B and increased COX-2 gene expression in rat hippocampus, which were inhibited by probiotics supplementation. Conclusions: Our findings suggest that probiotics may play a role in orofacial pain relief and cognitive enhancement in painful situations by modulating gut microbiota composition and influencing protein levels and gene expression in brain regions associated with pain and cognition.