Background: Osteoarthritis (OA) is the most common form of chronic pain in Europe (34%), representing a great economic and social cost to society. There are studies that suggest an intestine–brain–articulation axis and hint at the existence of low-grade intestinal inflammation in OA, which would be related to an alteration of the microbiota and to the impairment of the epithelial barrier, with leakage of the microbial components. Purpose: The purpose of this study was to review the association between gut microbiome and pain in the OA population through a review of the literature. Methods: A literature search was conducted to identify all available studies on the association between the gut microbiome and pain in the OA population, with no publication date limit until September 2020 and no language limit, in the MEDLINE, CINAHL, Web of Science and Cochrane Central Register of Controlled Trials databases. Results: Only three of 2084 studies detected and analyzed by performing the proposed searches in the detailed databases, were finally selected for this review, of which one was with and two were without intervention. These studies only weakly support a relationship between the gut microbiome and OA, specifically a correlation between certain taxa or microbial products and the inflammatory landscape and severity of OA symptoms, including knee pain. Conclusions: Despite encouraging results, this review highlights the paucity of high-quality studies addressing the potential role of the gut microbiome in OA-related pain, along with the disparity of the techniques used so far, making it impossible to draw firm conclusions on the topic.