The review focuses primarily on collating and analyzing the mechanistic research data that discusses the function of prebiotics to halt the frailty of musculoskeletal system. Musculoskeletal diseases (MSDs) are frequently reported to co-occur within their own categories of conditions, such as osteoarthritis, rheumatoid arthritis, gouty arthritis, and psoriatic arthritis owing to their overlapping pathogenesis. Consequently, the same drugs are often used to manage the complications of most types. A few recent studies have addressed the therapeutic functions of gut microbes toward those commonly shared MSD pathway targets. Improving microbial diversity and enriching their population in the gut would promote the regeneration and recovery of the musculoskeletal system. Prebiotics are usually nondigestible substrates that are selectively used or digested by the gut microbes conferring health promotion. The microbial fermentation of prebiotics generates numerous host-beneficial therapeutic molecules. This study inspects the presumptive functions of plant-derived prebiotics for the growth and restoration of intestinal microbiota and the consequent improvement of skeletal health. The review also highlights the discrete functions of prebiotics against inflammation, autoimmunity, infection, physiologic overloading mechanism, and aging-associated loss of metabolism in MSD.